Role of reactive oxygen species-elicited apoptosis in the pathophysiology of mitochondrial and neurodegenerative diseases associated with mitochondrial DNA mutations.
A wide spectrum of pathogenic mutations of mitochondrial DNA (mtDNA) has been demonstrated to cause mitochondrial dysfunction and overproduction of reactive oxygen species (ROS), in relation to mitochondrial and neurodegenerative diseases. Our previous studies have shown that large-scale deletions of mtDNA not only serve as an indicator of oxidative damage, but also result in greater susceptibility of human cells to apoptosis triggered by UV irradiation and other apoptotic stimuli. In this review, we focus on the involvement of mtDNA-mutation-associated oxidative stress and susceptibility to apoptosis in the pathophysiology of mitochondrial and neurodegenerative diseases. Different lines of research have provided concordant data to suggest that the mtDNA-mutation-elicited energy insufficiency and enhanced oxidative stress and damage lead to cell dysfunction, and increase the susceptibility of affected cells to apoptosis in patients with these diseases. Moreover, accumulating experimental evidence has shown that antioxidant therapy is a good strategy for decreasing intracellular ROS and alleviating oxidative-stress-induced apoptosis in cells of patients that harbor pathogenic mtDNA mutations.
Liu
Chun-Yi
CY
Institute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan.
Lee
Cheng-Feng
CF
Wei
Yau-Huei
YH
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D017209:Apoptosis; D004272:DNA, Mitochondrial / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000975:Antioxidants; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species