Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer’s disease(AD).The mitochondrial contact site and cristae organizing system(MICOS)plays a pivotal role in shaping the inner mitochondrial...Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer’s disease(AD).The mitochondrial contact site and cristae organizing system(MICOS)plays a pivotal role in shaping the inner mitochondrial membrane,forming cristae junctions and establishing interaction sites between the inner and outer mitochondrial membranes and thereby serving as a cornerstone of mitochondrial structure and function.In the past decade,MICOS abnormalities have been extensively linked to AD pathogenesis.In particular,dysregulated expression of MICOS subunits and mutations in MICOS-related genes have been identified in AD,often in association with hallmark pathological features such as amyloid-b plaque accumulation,neurofibrillary tangle formation,and neuronal apoptosis.Furthermore,MICOS subunits interact with several etiologically relevant proteins,significantly influencing AD progression.The intricate crosstalk between these proteins and MICOS subunits underscores the relevance of MICOS dysfunction in AD.Therapeutic strategies targeting MICOS subunits or their interacting proteins may offer novel approaches for AD treatment.In the present review,we introduce current understanding of MICOS structures and functions,highlight MICOS pathogenesis in AD,and summarize the available MICOS-targeting drugs potentially useful for AD.展开更多
基金funded by the National Natural Science Foundation of China(No.81500858 to Xinwen Zhang,No.81700977 to Xu Yan)Natural Science Foundation of Liaoning Province(China)(No.2022-MS-231 to Xinwen Zhang)+1 种基金the Science and Technology Planning Project of Shenyang(China)(No.22-321-33-26 to Dehao Shang)Grants-in-Aid for Scientific Research(Japan)(No.22K09927 to Zhou Wu).
文摘Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer’s disease(AD).The mitochondrial contact site and cristae organizing system(MICOS)plays a pivotal role in shaping the inner mitochondrial membrane,forming cristae junctions and establishing interaction sites between the inner and outer mitochondrial membranes and thereby serving as a cornerstone of mitochondrial structure and function.In the past decade,MICOS abnormalities have been extensively linked to AD pathogenesis.In particular,dysregulated expression of MICOS subunits and mutations in MICOS-related genes have been identified in AD,often in association with hallmark pathological features such as amyloid-b plaque accumulation,neurofibrillary tangle formation,and neuronal apoptosis.Furthermore,MICOS subunits interact with several etiologically relevant proteins,significantly influencing AD progression.The intricate crosstalk between these proteins and MICOS subunits underscores the relevance of MICOS dysfunction in AD.Therapeutic strategies targeting MICOS subunits or their interacting proteins may offer novel approaches for AD treatment.In the present review,we introduce current understanding of MICOS structures and functions,highlight MICOS pathogenesis in AD,and summarize the available MICOS-targeting drugs potentially useful for AD.
