Heat transport in one kind of double-bond linear chains of fullerenes (C60's) is investigated by the classical nonequilibrium molecular dynamics method. It is found that the negative differential thermal resistance...Heat transport in one kind of double-bond linear chains of fullerenes (C60's) is investigated by the classical nonequilibrium molecular dynamics method. It is found that the negative differential thermal resistance (NDTR) is more likely to occur at larger temperature difference and shorter length. In addition, with the increase of the length, the thermal conductivity of the chains increases, and NDTR region shrinks and vanishes in the end. The temperature profiles reveal that a large temperature jump exists at a high-temperature boundary of the chains when NDTR occurs. These results may be helpful for designing thermal devices where low-dimensional C60 polymers can be used.展开更多
Highly-efficient oxidation of 5-hydroxymethylfurtural(HMF) to 2,5-furandicarboxylic acid(FDCA) at low temperature with air as the oxidant is still challenging.Herein,inspired by the respirato ry electron transport cha...Highly-efficient oxidation of 5-hydroxymethylfurtural(HMF) to 2,5-furandicarboxylic acid(FDCA) at low temperature with air as the oxidant is still challenging.Herein,inspired by the respirato ry electron transport chain(ETC) of living cells mediated by electron carriers,we constructed artificial ETCs and transformed liquid flow fuel cells(LFFCs) to flexible reactors for efficient oxidation of HMF to produce FDCA under mild conditions.This LFFC reactor employed an electrodeposition modified nickel foam as an anode to promote HMF oxidation and(VO_(2))_(2)SO_(4) as a cathode electron carrier to facilitate the electron transfer to air.The reaction rate could be easily controlled by selecting the anode catalyst,adjusting the external loading and changing the cathodic electron carrier or oxidants.A maximal power density of 44.9 mW cm^(-2) at room temperature was achieved,while for FDCA production,short-circuit condition was preferred to achieve quick transfer of electrons.For a single batch operation with 0.1 M initial HMF,FDCA yield reached 97.1%.By fed-batch operation,FDCA concentration reached 144.5 g L^(-1) with a total yield of 96%.Ni^(2+)/Ni^(3+) redox couple was the active species mediating the electron transfer,while both experimental and DFT calculation results indicated that HMFCA pathway was the preferred reaction mechanism.展开更多
This study demonstrates a concentration dependent inhibition of carbon fixation, O2 evolution, photosynthetic electron transport chain and ATP content of A. doliolum and C. vulgaris by Cu, Ni and Fe. Although the mode...This study demonstrates a concentration dependent inhibition of carbon fixation, O2 evolution, photosynthetic electron transport chain and ATP content of A. doliolum and C. vulgaris by Cu, Ni and Fe. Although the mode of inhibition of photosynthetic electron transport chain of both the algae was similar, PS II depicted greater sensitivity to the test metals used. The toxicity in both organisms was Cu > Ni > Fe. A. doliolum was, however, more sensitive to Cu and Ni, and C. vulgaris to Fe. Toxicity was generally dependent on metal uptake, which in turn was dependent on their concentrations in the external medium. A partial restoration of nutrient uptake, carbon fixation, and enzyme activities following supplementation of exogenous ATP suggests that ATP regulates toxicity through chelation.展开更多
Using a transfer matrix method, we investigate spin transport through a chain of polygonal rings with Dresselhaus spin-orbit coupling(DSOC). The spin conductance is dependent on the number of sides in the polygons. ...Using a transfer matrix method, we investigate spin transport through a chain of polygonal rings with Dresselhaus spin-orbit coupling(DSOC). The spin conductance is dependent on the number of sides in the polygons. When DSOC is considered in a chain which also has Rashba spin-orbit coupling(RSOC) of the same magnitude, the total conductance is the same as that for the same chain with no SOC. However, when the two types of SOC have different values, there results a unique anisotropic conductance.展开更多
In two experiments, the effects of succinate and NADH(reduced nicotinamide adenine dinucleotide) on metmyoglobin reductase activity and electron transport chain-linked metmyoglobin reduction were investigated and co...In two experiments, the effects of succinate and NADH(reduced nicotinamide adenine dinucleotide) on metmyoglobin reductase activity and electron transport chain-linked metmyoglobin reduction were investigated and compared. In experiment 1, metmyoglobin(MetMb), substrate and inhibitors were incubated with mitochondria. Comparsion of the effects of succinate and NADH on MetMb reduction was investigated. The MetMb percentage in sample treated with 8 mol L-1 succinate decreased by about 69% after 3 h incubation, and the effect was inhibited by the addition of 10 mol L-1 electron transfer chain complex II inhibitor malonic acid; the MetMb percentage in samples treated with 2 mol L-1 NADH decreased by 56% and the effect was inhibited by the addition of 0.02 mol L-1 electron transport chain complex I inhibitor rotenone. These results indicated that electron transport chain played an important role in MetMb reduction. Both complex II and complex I take part in the MetMb reduction in mitochondria through different pathways. NADH-MetMb reduction system was less stable than succinateMetMb system. In experiment 2, the beef longissimus dorsi muscle was blended with different concentrations of succinate or NADH. Enhancing patties with higher concentration of succinate or NADH improved colour stability in vacuum packaged samples(P〈0.05). These results verified that mitochondria electron transport chain is related to the MetMb reduction in meat system.展开更多
Hypobaric hypoxia can cause severe brain damage and mitochondrial dysfunction, and is involved in hypoxic brain injury. However, little is currently known about the mechanisms responsible for mi- tochondrial dysfuncti...Hypobaric hypoxia can cause severe brain damage and mitochondrial dysfunction, and is involved in hypoxic brain injury. However, little is currently known about the mechanisms responsible for mi- tochondrial dysfunction in hypobaric hypoxic brain damage. In this study, a rat model of hypobaric hypoxic brain injury was established to investigate the molecular mechanisms associated with mi- tochondrial dysfunction. As revealed by two-dimensional electrophoresis analysis, 16, 21, and 36 differential protein spots in cerebral mitochondria were observed at 6, 12, and 24 hours post-hypobaric hypoxia, respectively. Furthermore, ten protein spots selected from each hypobaric hypoxia subgroup were similarly regulated and were identified by mass spectrometry. These de- tected proteins included dihydropyrimidinase-related protein 2, creatine kinase B-type, is- ovaleryI-CoA dehydrogenase, elongation factor Ts, ATP synthase beta-subunit, 3-mercaptopyruvate sulfurtransferase, electron transfer flavoprotein alpha-subunit, Chain A of 2-enoyI-CoA hydratase, NADH dehydrogenase iron-sulfur protein 8 and tropomyosin beta chain. These ten proteins are all involved in the electron transport chain and the function of ATP synthase. Our findings indicate that hypobaric hypoxia can induce the differential expression of several cerebral mitochondrial proteins, which are involved in the regulation of mitochondrial energy production.展开更多
Heat as a stressor of poultry has been studied extensively for many decades; it affects poultry production on a worldwide basis and has significant impact on well-being and production. More recently, the involvement o...Heat as a stressor of poultry has been studied extensively for many decades; it affects poultry production on a worldwide basis and has significant impact on well-being and production. More recently, the involvement of heat stress in inducing oxidative stress has received much interest. Oxidative stress is defined as the presence of reactive species in excess of the available antioxidant capacity of animal cells. Reactive species can modify several biologically cellular macromolecules and can interfere with cell signaling pathways. Furthermore, during the last decade, there has been an ever-increasing interest in the use of a wide array of natural feed-delivered phytochemicals that have potential antioxidant properties for poultry. In light of this, the current review aims to(1) summarize the mechanisms through which heat stress triggers excessive superoxide radical production in the mitochondrion and progresses into oxidative stress,(2) illustrate that this pathophysiology is dependent on the intensity and duration of heat stress,(3) present different nutritional strategies for mitigation of mitochondrial dysfunction, with particular focus on antioxidant phytochemicals.Oxidative stress that occurs with heat exposure can be manifest in all parts of the body; however, mitochondrial dysfunction underlies oxidative stress. In the initial phase of acute heat stress, mitochondrial substrate oxidation and electron transport chain activity are increased resulting in excessive superoxide production. During the later stage of acute heat stress, down-regulation of avian uncoupling protein worsens the oxidative stress situation causing mitochondrial dysfunction and tissue damage. Typically, antioxidant enzyme activities are upregulated. Chronic heat stress, however, leads to downsizing of mitochondrial metabolic oxidative capacity, up-regulation of avian uncoupling protein, a clear alteration in the pattern of antioxidant enzyme activities, and depletion of antioxidant reserves.Some phytochemicals, such as various types of flavonoids and related compounds, were shown to be beneficial in chronic heat-stressed poultry, but were less or not effective in non-heat-stressed counterparts. This supports the contention that antioxidant phytochemicals have potential under challenging conditions. Though substantial progress has been made in our understanding of the association between heat stress and oxidative stress, the means by which phytochemicals can alleviate oxidative stress have been sparsely explored.展开更多
Distribution and activity of mitochondda are key factors in neuronal development, synaptic plasticity and axogenesis. The majority of energy sources, necessary for cellular functions, originate from oxidative phosphor...Distribution and activity of mitochondda are key factors in neuronal development, synaptic plasticity and axogenesis. The majority of energy sources, necessary for cellular functions, originate from oxidative phosphorylation located in the inner mitochondrial membrane. The adenosine-5'- triphosphate production is regulated by many control mechanism-firstly by oxygen, substrate level, adenosine-5'-diphosphate level, mitochondrial membrane potential, and rate of coupling and proton leak. Recently, these mechanisms have been implemented by "second control mechanisms," such as reversible phosphorylation of the tricarboxylic acid cycle enzymes and electron transport chain complexes, aUosteric inhibition of cytochrome c oxidase, thyroid hormones, effects of fatty acids and uncoupling proteins. Impaired function of mitochondria is implicated in many diseases ranging from mitochondrial myopathies to bipolar disorder and schizophrenia. Mitochondrial dysfunctions are usually related to the ability of mitochondria to generate adenosine-5'-triphosphate in response to energy demands. Large amounts of reactive oxygen species are released by defective mitochondria similarly, decline of antioxidative enzyme activities (e.g. in the elderly) enhances reactive oxygen species production. We reviewed data concerning neuroplasticity, physiology, and control of mitochondrial oxidative phosphorylation and reactive oxygen species production.展开更多
Microcystin-RR (MC-RR) has been suggested to induce apoptosis in tobacco BY-2 cells through mitochondrial dysfunction including the loss of mitochondrial membrane potential . TO further elucidate the mechanisms invo...Microcystin-RR (MC-RR) has been suggested to induce apoptosis in tobacco BY-2 cells through mitochondrial dysfunction including the loss of mitochondrial membrane potential . TO further elucidate the mechanisms involved in MC-RR induced apoptosis in tobacco BY-2 cells, we have investigated the role of mitochondrial electron transport chain (ETC) as a potential source for reactive oxygen species (ROS). Tobacco BY-2 cells after exposure to MC-RR (60 mg/L) displayed apoptotic changes in association with an increased production of ROS and loss of Am. All of these adverse effects were significantly attenuated by ETC inhibitors including Rotenone (2 μmol/L, complex I inhibitor) and antimycin A (0.01 μmol/L, complex III inhibitor), but not by thenoyltrifluoroacetone (S μmol/L, complex Ⅱinhibitor). These results suggest that rnitochondrial ETC plays a key role in mediating MC-RR induced apoptosis in tobacco BY-2 cells through an increased mitochondrial production of ROS.展开更多
The primary function of mitochondria is respiration, where catabolism of substrates is coupled to ATP synthesis via oxidative phosphorylation. In plants, mitochondrial composition is relatively complex and flexible an...The primary function of mitochondria is respiration, where catabolism of substrates is coupled to ATP synthesis via oxidative phosphorylation. In plants, mitochondrial composition is relatively complex and flexible and has specific pathways to support photosynthetic processes in illuminated leaves.展开更多
Aging is by far the most prominent risk factor for Alzheimer’s disease(AD),and both aging and AD are associated with apparent metabolic alterations.As developing effective therapeutic interventions to treat AD is cle...Aging is by far the most prominent risk factor for Alzheimer’s disease(AD),and both aging and AD are associated with apparent metabolic alterations.As developing effective therapeutic interventions to treat AD is clearly in urgent need,the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients,on disease pathogenesis,have been explored.There is also an increasing awareness of differential risk and potential targeting strategies related to biological sex,microbiome,and circadian regulation.As a major part of intracellular metabolism,mitochondrial bioenergetics,mitochondrial quality-control mechanisms,and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions.This review summarizes and highlights these efforts.展开更多
Aging is a complex process that can be characterized by functional and cognitive decline in an individual. Aging can be assessed based on the functional capacity of vital organs and their intricate interactions with o...Aging is a complex process that can be characterized by functional and cognitive decline in an individual. Aging can be assessed based on the functional capacity of vital organs and their intricate interactions with one another. Thus, the nature of aging can be described by focusing on a specific organ and an individual itself. However, to fully understand the complexity of aging,one must investigate not only a single tissue or biological process but also its complex interplay and interdependencies with other biological processes. Here, using RNA-seq, we monitored changes in the transcriptome during aging in four tissues(including brain, blood, skin and liver) in mice at9 months, 15 months, and 24 months, with a final evaluation at the very old age of 30 months.We identified several genes and processes that were differentially regulated during aging in both tissue-dependent and tissue-independent manners. Most importantly, we found that the electron transport chain(ETC) of mitochondria was similarly affected at the transcriptome level in the four tissues during the aging process. We also identified the liver as the tissue showing the largest variety of differentially expressed genes(DEGs) over time. Lcn2(Lipocalin-2) was found to be similarly regulated among all tissues, and its effect on longevity and survival was validated using its orthologue in Caenorhabditis elegans. Our study demonstrated that the molecular processes of aging are relatively subtle in their progress, and the aging process of every tissue depends on the tissue’s specialized function and environment. Hence, individual gene or process alone cannot be described as the key of aging in the whole organism.展开更多
Respirasome,as a vital part of the oxidative phosphorylation system,undertakes the task of transferring electrons from the electron donors to oxygen and produces a proton concentration gradient across the inner mitoch...Respirasome,as a vital part of the oxidative phosphorylation system,undertakes the task of transferring electrons from the electron donors to oxygen and produces a proton concentration gradient across the inner mitochondrial membrane through the coupled translocation of protons.Copious research has been carried out on this lynchpin of respiration.From the discovery of individual respiratory complexes to the report of the high-resolution structure of mammalian respiratory supercomplex I1III2IV1,scientists have gradually uncovered the mysterious veil of the electron transport chain(ETC).With the discovery of the mammalian respiratory mega complex I2III2IV2,a new perspective emerges in the research field of the ETC.Behind these advances glitters the light of the revolution in both theory and technology.Here,we give a short review about how scientists‘see’the structure and the mechanism of respirasome from the macroscopic scale to the atomic scale during the past decades.展开更多
Buruli ulcer(BU),caused by Mycobacterium ulcerans,is currently treated with rifampin estreptomycin or rifampineclarithromycin daily for 8 weeks recommended by World Health Organization(WHO).These options are lengthy w...Buruli ulcer(BU),caused by Mycobacterium ulcerans,is currently treated with rifampin estreptomycin or rifampineclarithromycin daily for 8 weeks recommended by World Health Organization(WHO).These options are lengthy with severe side effects.A new anti-tuberculosis drug,TB47,targeting QcrB in cytochrome bc1:aa3 complex is being developed in China.TB47-containing regimens were evaluated in a well-established murine model using an autoluminescent M.ulcerans strain.Highlevel TB47-resistant spontaneous M.ulcerans mutants were selected and their qcrB genes were sequenced.The in vivo activities of TB47 against both low-level and high-level TB47-resistant mutants were tested in BU murine model.Here,we show that TB47-containing oral 3-drug regimens can completely cure BU in 2 weeks for daily use or in 3 weeks given twice per week(6 doses in total).All high-level TB47-resistant mutants could only be selected using the low-level mutants which were still sensitive to TB47 in mice.This is the first report of double mutations in QcrB in mycobacteria.In summary,TB47-containing regimens have promise to cure BU highly effectively and prevent the emergence of drug resistance.Novel QcrB mutations found here may guide the potential clinical molecular diagnosis of resistance and the discovery of new drugs against the high-level resistant mutants.展开更多
基金Supported by the National Natural Science Foundation of China under Grant Nos 11004082 and 11005048the Natural Science Foundation of Guangdong Province under Grant No 2014A030313367
文摘Heat transport in one kind of double-bond linear chains of fullerenes (C60's) is investigated by the classical nonequilibrium molecular dynamics method. It is found that the negative differential thermal resistance (NDTR) is more likely to occur at larger temperature difference and shorter length. In addition, with the increase of the length, the thermal conductivity of the chains increases, and NDTR region shrinks and vanishes in the end. The temperature profiles reveal that a large temperature jump exists at a high-temperature boundary of the chains when NDTR occurs. These results may be helpful for designing thermal devices where low-dimensional C60 polymers can be used.
基金supported by the National Key R&D Program of China(2022YFA2105900)the National Natural Science Foundation of China(22178197)。
文摘Highly-efficient oxidation of 5-hydroxymethylfurtural(HMF) to 2,5-furandicarboxylic acid(FDCA) at low temperature with air as the oxidant is still challenging.Herein,inspired by the respirato ry electron transport chain(ETC) of living cells mediated by electron carriers,we constructed artificial ETCs and transformed liquid flow fuel cells(LFFCs) to flexible reactors for efficient oxidation of HMF to produce FDCA under mild conditions.This LFFC reactor employed an electrodeposition modified nickel foam as an anode to promote HMF oxidation and(VO_(2))_(2)SO_(4) as a cathode electron carrier to facilitate the electron transfer to air.The reaction rate could be easily controlled by selecting the anode catalyst,adjusting the external loading and changing the cathodic electron carrier or oxidants.A maximal power density of 44.9 mW cm^(-2) at room temperature was achieved,while for FDCA production,short-circuit condition was preferred to achieve quick transfer of electrons.For a single batch operation with 0.1 M initial HMF,FDCA yield reached 97.1%.By fed-batch operation,FDCA concentration reached 144.5 g L^(-1) with a total yield of 96%.Ni^(2+)/Ni^(3+) redox couple was the active species mediating the electron transfer,while both experimental and DFT calculation results indicated that HMFCA pathway was the preferred reaction mechanism.
文摘This study demonstrates a concentration dependent inhibition of carbon fixation, O2 evolution, photosynthetic electron transport chain and ATP content of A. doliolum and C. vulgaris by Cu, Ni and Fe. Although the mode of inhibition of photosynthetic electron transport chain of both the algae was similar, PS II depicted greater sensitivity to the test metals used. The toxicity in both organisms was Cu > Ni > Fe. A. doliolum was, however, more sensitive to Cu and Ni, and C. vulgaris to Fe. Toxicity was generally dependent on metal uptake, which in turn was dependent on their concentrations in the external medium. A partial restoration of nutrient uptake, carbon fixation, and enzyme activities following supplementation of exogenous ATP suggests that ATP regulates toxicity through chelation.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.61176089 and 11504083)the Foundation of Shijiazhuang University,China(Grant No.XJPT002)
文摘Using a transfer matrix method, we investigate spin transport through a chain of polygonal rings with Dresselhaus spin-orbit coupling(DSOC). The spin conductance is dependent on the number of sides in the polygons. When DSOC is considered in a chain which also has Rashba spin-orbit coupling(RSOC) of the same magnitude, the total conductance is the same as that for the same chain with no SOC. However, when the two types of SOC have different values, there results a unique anisotropic conductance.
基金the National Natural Science Foundation of China (31071624)
文摘In two experiments, the effects of succinate and NADH(reduced nicotinamide adenine dinucleotide) on metmyoglobin reductase activity and electron transport chain-linked metmyoglobin reduction were investigated and compared. In experiment 1, metmyoglobin(MetMb), substrate and inhibitors were incubated with mitochondria. Comparsion of the effects of succinate and NADH on MetMb reduction was investigated. The MetMb percentage in sample treated with 8 mol L-1 succinate decreased by about 69% after 3 h incubation, and the effect was inhibited by the addition of 10 mol L-1 electron transfer chain complex II inhibitor malonic acid; the MetMb percentage in samples treated with 2 mol L-1 NADH decreased by 56% and the effect was inhibited by the addition of 0.02 mol L-1 electron transport chain complex I inhibitor rotenone. These results indicated that electron transport chain played an important role in MetMb reduction. Both complex II and complex I take part in the MetMb reduction in mitochondria through different pathways. NADH-MetMb reduction system was less stable than succinateMetMb system. In experiment 2, the beef longissimus dorsi muscle was blended with different concentrations of succinate or NADH. Enhancing patties with higher concentration of succinate or NADH improved colour stability in vacuum packaged samples(P〈0.05). These results verified that mitochondria electron transport chain is related to the MetMb reduction in meat system.
基金supported by the National Natural Science Foundation of China,No.81073152the Key Science Foundation of Tianjin in China,No.10JCZDJC21100+1 种基金the Natural Science Foundation of Tianjin in China,No.10JCYBJC14700,No.13JCQNJC13200the Science Foundation of Tianjin Key Laboratory in China,No.WHTD 201303-2
文摘Hypobaric hypoxia can cause severe brain damage and mitochondrial dysfunction, and is involved in hypoxic brain injury. However, little is currently known about the mechanisms responsible for mi- tochondrial dysfunction in hypobaric hypoxic brain damage. In this study, a rat model of hypobaric hypoxic brain injury was established to investigate the molecular mechanisms associated with mi- tochondrial dysfunction. As revealed by two-dimensional electrophoresis analysis, 16, 21, and 36 differential protein spots in cerebral mitochondria were observed at 6, 12, and 24 hours post-hypobaric hypoxia, respectively. Furthermore, ten protein spots selected from each hypobaric hypoxia subgroup were similarly regulated and were identified by mass spectrometry. These de- tected proteins included dihydropyrimidinase-related protein 2, creatine kinase B-type, is- ovaleryI-CoA dehydrogenase, elongation factor Ts, ATP synthase beta-subunit, 3-mercaptopyruvate sulfurtransferase, electron transfer flavoprotein alpha-subunit, Chain A of 2-enoyI-CoA hydratase, NADH dehydrogenase iron-sulfur protein 8 and tropomyosin beta chain. These ten proteins are all involved in the electron transport chain and the function of ATP synthase. Our findings indicate that hypobaric hypoxia can induce the differential expression of several cerebral mitochondrial proteins, which are involved in the regulation of mitochondrial energy production.
基金the Special Research Fund(BOF)of Ghent University(Belgium)for the financial support of Abdol ah Akbarian(grant number 01SF2711)
文摘Heat as a stressor of poultry has been studied extensively for many decades; it affects poultry production on a worldwide basis and has significant impact on well-being and production. More recently, the involvement of heat stress in inducing oxidative stress has received much interest. Oxidative stress is defined as the presence of reactive species in excess of the available antioxidant capacity of animal cells. Reactive species can modify several biologically cellular macromolecules and can interfere with cell signaling pathways. Furthermore, during the last decade, there has been an ever-increasing interest in the use of a wide array of natural feed-delivered phytochemicals that have potential antioxidant properties for poultry. In light of this, the current review aims to(1) summarize the mechanisms through which heat stress triggers excessive superoxide radical production in the mitochondrion and progresses into oxidative stress,(2) illustrate that this pathophysiology is dependent on the intensity and duration of heat stress,(3) present different nutritional strategies for mitigation of mitochondrial dysfunction, with particular focus on antioxidant phytochemicals.Oxidative stress that occurs with heat exposure can be manifest in all parts of the body; however, mitochondrial dysfunction underlies oxidative stress. In the initial phase of acute heat stress, mitochondrial substrate oxidation and electron transport chain activity are increased resulting in excessive superoxide production. During the later stage of acute heat stress, down-regulation of avian uncoupling protein worsens the oxidative stress situation causing mitochondrial dysfunction and tissue damage. Typically, antioxidant enzyme activities are upregulated. Chronic heat stress, however, leads to downsizing of mitochondrial metabolic oxidative capacity, up-regulation of avian uncoupling protein, a clear alteration in the pattern of antioxidant enzyme activities, and depletion of antioxidant reserves.Some phytochemicals, such as various types of flavonoids and related compounds, were shown to be beneficial in chronic heat-stressed poultry, but were less or not effective in non-heat-stressed counterparts. This supports the contention that antioxidant phytochemicals have potential under challenging conditions. Though substantial progress has been made in our understanding of the association between heat stress and oxidative stress, the means by which phytochemicals can alleviate oxidative stress have been sparsely explored.
基金supported by grant NoMSM0021620849 given by the Ministry of Education,Youth and Sports of the Czech Republicby project PRVOUK-P26/LF1/4given by Charles University in Prague+1 种基金by grant No. SVV-2012-264514 from Charles University in Pragueby grant No.41310 given by the Grant Agency of Charles University in Prague,Czech Republic
文摘Distribution and activity of mitochondda are key factors in neuronal development, synaptic plasticity and axogenesis. The majority of energy sources, necessary for cellular functions, originate from oxidative phosphorylation located in the inner mitochondrial membrane. The adenosine-5'- triphosphate production is regulated by many control mechanism-firstly by oxygen, substrate level, adenosine-5'-diphosphate level, mitochondrial membrane potential, and rate of coupling and proton leak. Recently, these mechanisms have been implemented by "second control mechanisms," such as reversible phosphorylation of the tricarboxylic acid cycle enzymes and electron transport chain complexes, aUosteric inhibition of cytochrome c oxidase, thyroid hormones, effects of fatty acids and uncoupling proteins. Impaired function of mitochondria is implicated in many diseases ranging from mitochondrial myopathies to bipolar disorder and schizophrenia. Mitochondrial dysfunctions are usually related to the ability of mitochondria to generate adenosine-5'-triphosphate in response to energy demands. Large amounts of reactive oxygen species are released by defective mitochondria similarly, decline of antioxidative enzyme activities (e.g. in the elderly) enhances reactive oxygen species production. We reviewed data concerning neuroplasticity, physiology, and control of mitochondrial oxidative phosphorylation and reactive oxygen species production.
基金supported by the National Natural Science Foundation of China (No.31100340)the Major Science and Technology Program for Water Pollution Control and Treatment (No.2012ZX07103-004-02)
文摘Microcystin-RR (MC-RR) has been suggested to induce apoptosis in tobacco BY-2 cells through mitochondrial dysfunction including the loss of mitochondrial membrane potential . TO further elucidate the mechanisms involved in MC-RR induced apoptosis in tobacco BY-2 cells, we have investigated the role of mitochondrial electron transport chain (ETC) as a potential source for reactive oxygen species (ROS). Tobacco BY-2 cells after exposure to MC-RR (60 mg/L) displayed apoptotic changes in association with an increased production of ROS and loss of Am. All of these adverse effects were significantly attenuated by ETC inhibitors including Rotenone (2 μmol/L, complex I inhibitor) and antimycin A (0.01 μmol/L, complex III inhibitor), but not by thenoyltrifluoroacetone (S μmol/L, complex Ⅱinhibitor). These results suggest that rnitochondrial ETC plays a key role in mediating MC-RR induced apoptosis in tobacco BY-2 cells through an increased mitochondrial production of ROS.
基金supported by the Australian Research Council (ARC) ARC Centre of Excellence for Plant Energy Biology(CE0561495)RPJ is supported by a Grains Research and Development Corporation (GRDC) PhD scholarship+1 种基金LL was funded by Scholarship International Research Fees (SIRF),University International Stipend (UIS) and a Top Up Scholarship for UISAHM is supported by the Australian Research Council(ARC) as an ARC Future Fellow
文摘The primary function of mitochondria is respiration, where catabolism of substrates is coupled to ATP synthesis via oxidative phosphorylation. In plants, mitochondrial composition is relatively complex and flexible and has specific pathways to support photosynthetic processes in illuminated leaves.
基金the UAB NSC P30 AG05886(SA,SB,TB,CC,DLS,VDU,JZ)for partial support。
文摘Aging is by far the most prominent risk factor for Alzheimer’s disease(AD),and both aging and AD are associated with apparent metabolic alterations.As developing effective therapeutic interventions to treat AD is clearly in urgent need,the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients,on disease pathogenesis,have been explored.There is also an increasing awareness of differential risk and potential targeting strategies related to biological sex,microbiome,and circadian regulation.As a major part of intracellular metabolism,mitochondrial bioenergetics,mitochondrial quality-control mechanisms,and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions.This review summarizes and highlights these efforts.
基金supported by the Deutsche Forschungsgemeinschaft(DFG)for 1738 B2the Bundesministerum fuer Bildung und Forschung(BMBF)Bernstein Fokus(Grant No.01GQ0923)+2 种基金the BMBF Gerontosys JenAge(Grant No.0315581A/B)the EU BrainAge(Grant Nos.FP7/HEALTH.2011.2.2.2-2 and 279281)the BMBF Irestra(Grant No.16SV7209)
文摘Aging is a complex process that can be characterized by functional and cognitive decline in an individual. Aging can be assessed based on the functional capacity of vital organs and their intricate interactions with one another. Thus, the nature of aging can be described by focusing on a specific organ and an individual itself. However, to fully understand the complexity of aging,one must investigate not only a single tissue or biological process but also its complex interplay and interdependencies with other biological processes. Here, using RNA-seq, we monitored changes in the transcriptome during aging in four tissues(including brain, blood, skin and liver) in mice at9 months, 15 months, and 24 months, with a final evaluation at the very old age of 30 months.We identified several genes and processes that were differentially regulated during aging in both tissue-dependent and tissue-independent manners. Most importantly, we found that the electron transport chain(ETC) of mitochondria was similarly affected at the transcriptome level in the four tissues during the aging process. We also identified the liver as the tissue showing the largest variety of differentially expressed genes(DEGs) over time. Lcn2(Lipocalin-2) was found to be similarly regulated among all tissues, and its effect on longevity and survival was validated using its orthologue in Caenorhabditis elegans. Our study demonstrated that the molecular processes of aging are relatively subtle in their progress, and the aging process of every tissue depends on the tissue’s specialized function and environment. Hence, individual gene or process alone cannot be described as the key of aging in the whole organism.
基金Tsinghua University Branch of China National Center for Protein Sciences(Beijing)for providing the facility support.
文摘Respirasome,as a vital part of the oxidative phosphorylation system,undertakes the task of transferring electrons from the electron donors to oxygen and produces a proton concentration gradient across the inner mitochondrial membrane through the coupled translocation of protons.Copious research has been carried out on this lynchpin of respiration.From the discovery of individual respiratory complexes to the report of the high-resolution structure of mammalian respiratory supercomplex I1III2IV1,scientists have gradually uncovered the mysterious veil of the electron transport chain(ETC).With the discovery of the mammalian respiratory mega complex I2III2IV2,a new perspective emerges in the research field of the ETC.Behind these advances glitters the light of the revolution in both theory and technology.Here,we give a short review about how scientists‘see’the structure and the mechanism of respirasome from the macroscopic scale to the atomic scale during the past decades.
基金supported by the National Mega-Project of China for Innovative Drugs(2019ZX09721001-003-003)the Chinese Academy of Sciences grant(154144KYSB20190005,China)+2 种基金the Key-Area Research and Development Program of Guangdong Province(2019B110233003,China)the Special Funds for Economic Development of Marine Economy of Guangdong Province(GDME-2018C003,China)partially by the Grants(SKLRDOP-201919 and SKLRD-Z-202016)from the State Key Laboratory of Respiratory Disease,Guangzhou Institute of Respiratory Diseases,First Affiliated Hospital of Guangzhou Medical University,Guangzhou,China。
文摘Buruli ulcer(BU),caused by Mycobacterium ulcerans,is currently treated with rifampin estreptomycin or rifampineclarithromycin daily for 8 weeks recommended by World Health Organization(WHO).These options are lengthy with severe side effects.A new anti-tuberculosis drug,TB47,targeting QcrB in cytochrome bc1:aa3 complex is being developed in China.TB47-containing regimens were evaluated in a well-established murine model using an autoluminescent M.ulcerans strain.Highlevel TB47-resistant spontaneous M.ulcerans mutants were selected and their qcrB genes were sequenced.The in vivo activities of TB47 against both low-level and high-level TB47-resistant mutants were tested in BU murine model.Here,we show that TB47-containing oral 3-drug regimens can completely cure BU in 2 weeks for daily use or in 3 weeks given twice per week(6 doses in total).All high-level TB47-resistant mutants could only be selected using the low-level mutants which were still sensitive to TB47 in mice.This is the first report of double mutations in QcrB in mycobacteria.In summary,TB47-containing regimens have promise to cure BU highly effectively and prevent the emergence of drug resistance.Novel QcrB mutations found here may guide the potential clinical molecular diagnosis of resistance and the discovery of new drugs against the high-level resistant mutants.