Amyotrophic lateral sclerosis(ALS)is the most common motor neuron disease characterized by progressive loss of motor neurons in the brainstem and spinal cord.Currently,there is no cure or effective treatment for ALS a...Amyotrophic lateral sclerosis(ALS)is the most common motor neuron disease characterized by progressive loss of motor neurons in the brainstem and spinal cord.Currently,there is no cure or effective treatment for ALS and the cause of disease is unknown in the majority of ALS cases.Neuronal mitochondria dysfunction is one of the earliest features of ALS.Mitochondria are highly dynamic organelles that undergo continuous fission,fusion,trafficking and turnover,all of which contribute to the maintenance of mitochondrial function.Abnormal mitochondrial dynamics have been repeatedly reported in ALS and increasing evidence suggests altered mitochondrial dynamics as possible pathomechanisms underlying mitochondrial dysfunction in ALS.Here,we provide an overview of mitochondrial dysfunction and dynamic abnormalities observed in ALS,and discuss the possibility of targeting mitochondrial dynamics as a novel therapeutic approach for ALS.展开更多
Ischemia/reperfusion(I/R)injury inevitably occurs during liver resection and transplantation.Elderly patients poorly recover from these surgeries.This reduced reparative capacity with aging is causatively associated w...Ischemia/reperfusion(I/R)injury inevitably occurs during liver resection and transplantation.Elderly patients poorly recover from these surgeries.This reduced reparative capacity with aging is causatively associated with decreased mitochondrial function after reperfusion.Mitochondrial autophagy(mitophagy)is a vital cellular process that timely clears abnormal and dysfunctional mitochondria.Impaired or insufficient autophagy can contribute to hepatocyte death after I/R.This review describes our current understanding of I/R injury and highlights new mechanistic correlation between sirtuin 1(SIRT1),mitofusin 2(MFN2),and autophagy in the pathogenesis of age-dependent hypersensitivity to reperfusion injury.The deacetylation of MFN2 by SIRT1 plays a pivotal role in the recovery from reperfusion injury by modulating the onset of autophagy.Targeting the SIRT1-MFN2 axis could be a new therapeutic target to reduce I/R injury in aged livers.展开更多
基金by grants from National Institutes of Health(R03AG044680,R21NS085747 and R01NS089604)Alzheimer’s Association(2014-NIRG-301299).
文摘Amyotrophic lateral sclerosis(ALS)is the most common motor neuron disease characterized by progressive loss of motor neurons in the brainstem and spinal cord.Currently,there is no cure or effective treatment for ALS and the cause of disease is unknown in the majority of ALS cases.Neuronal mitochondria dysfunction is one of the earliest features of ALS.Mitochondria are highly dynamic organelles that undergo continuous fission,fusion,trafficking and turnover,all of which contribute to the maintenance of mitochondrial function.Abnormal mitochondrial dynamics have been repeatedly reported in ALS and increasing evidence suggests altered mitochondrial dynamics as possible pathomechanisms underlying mitochondrial dysfunction in ALS.Here,we provide an overview of mitochondrial dysfunction and dynamic abnormalities observed in ALS,and discuss the possibility of targeting mitochondrial dynamics as a novel therapeutic approach for ALS.
基金This work was supported by the USA National Institutes Health(NIH)grants R01 DK079878 and R01 DK09011504.
文摘Ischemia/reperfusion(I/R)injury inevitably occurs during liver resection and transplantation.Elderly patients poorly recover from these surgeries.This reduced reparative capacity with aging is causatively associated with decreased mitochondrial function after reperfusion.Mitochondrial autophagy(mitophagy)is a vital cellular process that timely clears abnormal and dysfunctional mitochondria.Impaired or insufficient autophagy can contribute to hepatocyte death after I/R.This review describes our current understanding of I/R injury and highlights new mechanistic correlation between sirtuin 1(SIRT1),mitofusin 2(MFN2),and autophagy in the pathogenesis of age-dependent hypersensitivity to reperfusion injury.The deacetylation of MFN2 by SIRT1 plays a pivotal role in the recovery from reperfusion injury by modulating the onset of autophagy.Targeting the SIRT1-MFN2 axis could be a new therapeutic target to reduce I/R injury in aged livers.
