Cardiolipin （CL） is a phospholipid exclusively localized in inner mitochondrial membrane where it is required for oxidative phosphorylation, ATP synthesis, and mitochondrial bioenergetics. The biological functions o...Cardiolipin （CL） is a phospholipid exclusively localized in inner mitochondrial membrane where it is required for oxidative phosphorylation, ATP synthesis, and mitochondrial bioenergetics. The biological functions of CL are thought to depend on its acyl chain composition which is dominated by linoleic acids in metabolically active tissues. This unique feature is not derived from the de novo biosynthesis of CL, rather from a remodeling process that involves in phospholipases and transacylase/acyltransferase. The remodeling process is also believed to be responsible for generation of CL species that causes oxidative stress and mitochondrial dysfunction. CL is highly sensitive to oxidative damages by reactive oxygen species （ROS） due to its high content in polyunsaturated fatty acids and location near the site of ROS production. Consequently, pathological remodeling of CL has been implicated in the etiology of mitochondrial dysfunction commonly associated with diabetes, obesity, heart failure, neurodegeneration, and aging that are characterized by oxidative stress, CL deficiency, and abnormal CL species. This review summarizes recent progresses in molecular, enzymatic, lipidomic, and metabolic studies that support a critical regulatory role of pathological CL remodeling as a missing link between oxidative stress and mitochondrial dysfunction in metabolic diseases and aging.展开更多
Mitochondrial redox metabolism has long been recognized as being central to the effects of aging and the development of age-related pathologies in the major oxidative organs. Consistent evidence has shown that exercis...Mitochondrial redox metabolism has long been recognized as being central to the effects of aging and the development of age-related pathologies in the major oxidative organs. Consistent evidence has shown that exercise is able to retard the onset and impede the progression of aging by modifying mitochondrial oxidant--antioxidant homeostasis. Here we provide a broad overview of the research evidence showing the relationship between mitochondrial redox metabolism, aging and exercise. We address part aspects of mitochondrial reactive oxygen species （ROS） metabolism, from superoxide production to ROS detoxification, especially antioxidant enzymes and uncoupling protein. Furthermore, we describe mitochondrial remodeling response to aging and exercise, which is accompanied by bioenergetics and redox regulation. In addition, potential mechanisms for redox signaling involved in mitochondrial remodeling and redox metabolism regulation are also reviewed.展开更多
基金supported in part by grants NIH(DK076685,Y.S.)Pennsylvania Department of Health using Tobacco Settlement Funds(10-K-273,Y.S.)
文摘Cardiolipin （CL） is a phospholipid exclusively localized in inner mitochondrial membrane where it is required for oxidative phosphorylation, ATP synthesis, and mitochondrial bioenergetics. The biological functions of CL are thought to depend on its acyl chain composition which is dominated by linoleic acids in metabolically active tissues. This unique feature is not derived from the de novo biosynthesis of CL, rather from a remodeling process that involves in phospholipases and transacylase/acyltransferase. The remodeling process is also believed to be responsible for generation of CL species that causes oxidative stress and mitochondrial dysfunction. CL is highly sensitive to oxidative damages by reactive oxygen species （ROS） due to its high content in polyunsaturated fatty acids and location near the site of ROS production. Consequently, pathological remodeling of CL has been implicated in the etiology of mitochondrial dysfunction commonly associated with diabetes, obesity, heart failure, neurodegeneration, and aging that are characterized by oxidative stress, CL deficiency, and abnormal CL species. This review summarizes recent progresses in molecular, enzymatic, lipidomic, and metabolic studies that support a critical regulatory role of pathological CL remodeling as a missing link between oxidative stress and mitochondrial dysfunction in metabolic diseases and aging.
基金supported by research grants from the National Natural Science Foundation of China(No.31110103919, 31200894,31000523,30771048,30470837,31071040,and 30270638)Tianjin Municipal Sci-tech-innovation Base Project (No.10SYSYJC28400)+1 种基金Tianjin Science and Technology Planning Project(No.12JCQNJC07900)General Administration of Sport of China Basic Project(No.10B058)
文摘Mitochondrial redox metabolism has long been recognized as being central to the effects of aging and the development of age-related pathologies in the major oxidative organs. Consistent evidence has shown that exercise is able to retard the onset and impede the progression of aging by modifying mitochondrial oxidant--antioxidant homeostasis. Here we provide a broad overview of the research evidence showing the relationship between mitochondrial redox metabolism, aging and exercise. We address part aspects of mitochondrial reactive oxygen species （ROS） metabolism, from superoxide production to ROS detoxification, especially antioxidant enzymes and uncoupling protein. Furthermore, we describe mitochondrial remodeling response to aging and exercise, which is accompanied by bioenergetics and redox regulation. In addition, potential mechanisms for redox signaling involved in mitochondrial remodeling and redox metabolism regulation are also reviewed.
