Mitochondrial oxidative stress, cellular damages and stem cell aging in premature aging models with complex II electron transport defect.

Abstract

Mitochondria which are the major intracellular reactive oxygen species (ROS) sources produce especially superoxide anion (O₂ ^•-) as a byproduct of energy production. It has been well known that O₂ ^•- is converted from oxygen (O₂) and is overproduced by excessive electron leakage from the mitochondrial electron transport chain (ETC), mainly complexes I and III. However we have previously reported that several point mutations (specifically G71E in C. elegans, I71E in Drosophila and V69E in mouse) in succinate dehydrogenase C subunit (SDHC) of complex II cause mitochondrial electron transport defect leading to O₂ ^•- overproduction from mitochondria. These mutations can cause endogenous oxidative stress resulting in tumorigenesis and apoptosis as well as premature death. Recently, we have also demonstrated that premature aging of hematopoietic stem cell with a mutation in SDHC is developed after the growth phase and normal development. Here, we review cellular damages by complex II electron transport defect-induced endogenous oxidative stress in premature aging models.