Elaidic acid(EA)stimulation can lead to endoplasmic reticulum stress(ERS),accompanied by a large release of Ca^(2+),and ultimately the activation of NLRP3 inflammasome in Kupffer cells(KCs).Mitochondrial instability o...Elaidic acid(EA)stimulation can lead to endoplasmic reticulum stress(ERS),accompanied by a large release of Ca^(2+),and ultimately the activation of NLRP3 inflammasome in Kupffer cells(KCs).Mitochondrial instability or dysfunction may be the key stimulating factors to activate NLRP3 inflammasome,and sustained Ca^(2+)transfer can result in mitochondrial dysfunction.We focused on KCs to explore the damage to mitochondria by EA.After EA stimulation,cells produced an oxidative stress(OS)response with a significant increase in ROS release.Immunoprecipitation experiments and the addition of inhibitors revealed that the increase in the level of intracellular Ca^(2+)led to Ca^(2+)accumulation in the mitochondrial matrix via mitochondria-associated membranes(MAMs).This was accompanied by a significant release of m ROS,loss of MMP and ATP,and a significant increase in mitochondrial permeability transition pore opening,ultimately leading to mitochondrial instability.These findings confirmed the mechanism that EA induced mitochondrial Ca^(2+)imbalance in KCs via MAM,ultimately leading to mitochondrial dysfunction.Meanwhile,EA induced OS and the decrease of MMP and ATP in rat liver,and significant lesions were found in liver mitochondria.Swelling of the inner mitochondrial cristae and mitochondrial vacuolization occurred,with a marked increase in lipid droplets.展开更多
The endoplasmic reticulum(ER)is connected to mitochondria through mitochondria-associated ER membranes(MAMs).MAMs provide a framework for crosstalk between the ER and mitochondria,playing a crucial role in regulating ...The endoplasmic reticulum(ER)is connected to mitochondria through mitochondria-associated ER membranes(MAMs).MAMs provide a framework for crosstalk between the ER and mitochondria,playing a crucial role in regulating cellular calcium balance,lipid metabolism,and cell death.Dysregulation of MAMs is involved in the development of chronic liver disease(CLD).In CLD,changes in MAMs structure and function occur due to factors such as cellular stress,inflammation,and oxidative stress,leading to abnormal interactions between mitochondria and the ER,resulting in liver cell injury,fibrosis,and impaired liver function.Traditional Chinese medicine has shown some research progress in regulating MAMs signaling and treating CLD.This paper reviews the literature on the association between mitochondria and the ER,as well as the intervention of traditional Chinese medicine in regulating CLD.展开更多
The endoplasmic reticulum(ER),which is composed of a continuous network of tubules and sheets,forms the most widely distributed membrane system in eukaryotic cells.As a result,it engages a variety of organelles by est...The endoplasmic reticulum(ER),which is composed of a continuous network of tubules and sheets,forms the most widely distributed membrane system in eukaryotic cells.As a result,it engages a variety of organelles by establishing membrane contact sites(MCSs).These contacts regulate organelle positioning and remodeling,including fusion and fission,facilitate precise lipid exchange,and couple vital signaling events.Here,we systematically review recent advances and converging themes on ER-involved organellar contact.The molecular basis,cellular influence,and potential physiological functions for ER/nuclear envelope contacts with mitochondria,Golgi,endosomes,lysosomes,lipid droplets,autophagosomes,and plasma membrane are summarized.展开更多
The ultimate goal in phosphoinositides cellular metabolism is to decipher their global functional organization and coordination of the com- partmentalized signaling processes. In this report we present evidence linkin...The ultimate goal in phosphoinositides cellular metabolism is to decipher their global functional organization and coordination of the com- partmentalized signaling processes. In this report we present evidence linking nuclear phos- phoinositides cycle with endoplasmic reticulum synthesis and function. The rapid transformation of [3H]inositol-labeled phosphoinositides in the intact nuclei (IN) was captured in chase studies for 0-5 min, followed by examination of phosphatidylinositides in the inner nuclear me- mbrane (INM), the outer nuclear membrane (ONM) and endoplasmic reticulum (ER). We revealed that synthesis of phosphatidylinositol phosphates (PIPs) occurs in ONM and the de- phosphorylation takes place in the INM. The rapid transformation of the radiolabeled PIPs in ONM reverberated in their appearance and successive transformation in INM, and in the 5min chased nuclei was tracked to ONM as the re- emerging radiolabeled phosphatidylinositol (PI). These chase-uncovered changes in ONM and INM PIPs profiles allow us to conclude that the observed conversions in the nuclear membrane continuum are induced by the lateral movement of the membrane and its transit from the cytosolic to nuclear and back to cytosolic environment. The suggested membrane synthesisinduced movement provides the means to transport the membrane- and the membrane lipid ligand-associated cytosolic proteins to the intranuclear spaces and renewal of INM. Export of the nuclear components interacting with the modified INM, by exiting from nuclear to cytosolic site, endows ER with a steady influx of the membrane that is conditioned to generate vesicles according to the nucleus delivered templates.展开更多
基金supported by fund from the National Natural Science Foundation of China(32172322)。
文摘Elaidic acid(EA)stimulation can lead to endoplasmic reticulum stress(ERS),accompanied by a large release of Ca^(2+),and ultimately the activation of NLRP3 inflammasome in Kupffer cells(KCs).Mitochondrial instability or dysfunction may be the key stimulating factors to activate NLRP3 inflammasome,and sustained Ca^(2+)transfer can result in mitochondrial dysfunction.We focused on KCs to explore the damage to mitochondria by EA.After EA stimulation,cells produced an oxidative stress(OS)response with a significant increase in ROS release.Immunoprecipitation experiments and the addition of inhibitors revealed that the increase in the level of intracellular Ca^(2+)led to Ca^(2+)accumulation in the mitochondrial matrix via mitochondria-associated membranes(MAMs).This was accompanied by a significant release of m ROS,loss of MMP and ATP,and a significant increase in mitochondrial permeability transition pore opening,ultimately leading to mitochondrial instability.These findings confirmed the mechanism that EA induced mitochondrial Ca^(2+)imbalance in KCs via MAM,ultimately leading to mitochondrial dysfunction.Meanwhile,EA induced OS and the decrease of MMP and ATP in rat liver,and significant lesions were found in liver mitochondria.Swelling of the inner mitochondrial cristae and mitochondrial vacuolization occurred,with a marked increase in lipid droplets.
基金Supported by the National Natural Science Foundation of China,No.82204755,and No.81960751the Guangxi Natural Science Foundation Youth Project,No.2023GXNSFBA026274+1 种基金the Guangxi University of Traditional Chinese Medicine School-level Project Youth Fund,No.2022QN008Faculty of Chinese Medicine Science Guangxi University of Chinese Medicine Research Project,No.2022MS008 and No.2022QJ001.
文摘The endoplasmic reticulum(ER)is connected to mitochondria through mitochondria-associated ER membranes(MAMs).MAMs provide a framework for crosstalk between the ER and mitochondria,playing a crucial role in regulating cellular calcium balance,lipid metabolism,and cell death.Dysregulation of MAMs is involved in the development of chronic liver disease(CLD).In CLD,changes in MAMs structure and function occur due to factors such as cellular stress,inflammation,and oxidative stress,leading to abnormal interactions between mitochondria and the ER,resulting in liver cell injury,fibrosis,and impaired liver function.Traditional Chinese medicine has shown some research progress in regulating MAMs signaling and treating CLD.This paper reviews the literature on the association between mitochondria and the ER,as well as the intervention of traditional Chinese medicine in regulating CLD.
基金supported by the National Natural Science Foundation of China(92254305)supported by the National Natural Science Foundation of China(92254305,91854204,32130026)+20 种基金supported by National Natural Science Foundation of China(92254302,32225013,32130023)supported by the National Natural Science Foundation of China(91954201,31971289)supported by grants from the National Natural Science Foundation of China(91954207)supported by the National Natural Science Foundation of China(32170753)supported by the National Natural Science Foundation of China(32170692,92154001)supported by grants from the National Natural Science Foundation of China(92254303,32170701)supported by grants from the National Natural Science Foundation of China(32101000,32271273)the Strategic Priority Research Program(XDB39000000)Project for Young Scientists in Basic Research(YSBR-075)of the Chinese Academy of Sciencesthe National Key Research and Development Program of China(2021YFA1300800)National Key Research and Development Program of China(2021YFA0804802,2019YFA0508602)Beijing Natural Science Foundation(JQ20028)New Cornerstone Science Foundation(Xplorer Prize)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB37020304)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB37040402)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA24030205)the National Key Research and Development Program of China(2021YFA1300301)the National Key Research and Development Program of China(2018YFA0506902)the Fundamental Research Funds for the Central Universities(63213104,63223043)the Talent Training Project at Nankai University(035-BB042112)supported by the Beijing Municipal Science&Technology Commission(5202022)。
文摘The endoplasmic reticulum(ER),which is composed of a continuous network of tubules and sheets,forms the most widely distributed membrane system in eukaryotic cells.As a result,it engages a variety of organelles by establishing membrane contact sites(MCSs).These contacts regulate organelle positioning and remodeling,including fusion and fission,facilitate precise lipid exchange,and couple vital signaling events.Here,we systematically review recent advances and converging themes on ER-involved organellar contact.The molecular basis,cellular influence,and potential physiological functions for ER/nuclear envelope contacts with mitochondria,Golgi,endosomes,lysosomes,lipid droplets,autophagosomes,and plasma membrane are summarized.
文摘The ultimate goal in phosphoinositides cellular metabolism is to decipher their global functional organization and coordination of the com- partmentalized signaling processes. In this report we present evidence linking nuclear phos- phoinositides cycle with endoplasmic reticulum synthesis and function. The rapid transformation of [3H]inositol-labeled phosphoinositides in the intact nuclei (IN) was captured in chase studies for 0-5 min, followed by examination of phosphatidylinositides in the inner nuclear me- mbrane (INM), the outer nuclear membrane (ONM) and endoplasmic reticulum (ER). We revealed that synthesis of phosphatidylinositol phosphates (PIPs) occurs in ONM and the de- phosphorylation takes place in the INM. The rapid transformation of the radiolabeled PIPs in ONM reverberated in their appearance and successive transformation in INM, and in the 5min chased nuclei was tracked to ONM as the re- emerging radiolabeled phosphatidylinositol (PI). These chase-uncovered changes in ONM and INM PIPs profiles allow us to conclude that the observed conversions in the nuclear membrane continuum are induced by the lateral movement of the membrane and its transit from the cytosolic to nuclear and back to cytosolic environment. The suggested membrane synthesisinduced movement provides the means to transport the membrane- and the membrane lipid ligand-associated cytosolic proteins to the intranuclear spaces and renewal of INM. Export of the nuclear components interacting with the modified INM, by exiting from nuclear to cytosolic site, endows ER with a steady influx of the membrane that is conditioned to generate vesicles according to the nucleus delivered templates.
