Identification of respiratory chain gene mutations that shorten replicative life span in yeast

Aging is the progressive accumulation of alterations in cells that elevates the risk of death. The mitochondrial theory of aging postulates that free radicals produced by the mitochondrial respiratory system contribute to the aging process. However, the roles of individual electron transfer chain (ETC) components in cellular aging have not been elucidated. In this study, we analyzed the replicative life span of 73 yeast deletion mutants lacking the genes of the mitochondrial electron transfer chain system, and found that nine of these mutants (Δnde1, Δtcm62, Δrip1, Δcyt1, Δqrc8, Δpet117, Δcox11, Δatp11, Δfmc1) had significantly shorter life spans. These mutants had lower rates of respiration and were slightly sensitive to exogenous administration of hydrogen peroxide. However, only two of them, Δnde1 and Δfmc1, produced higher amounts of intrinsic superoxide radicals in the presence of glucose compared to that of wild type cells. Interestingly, there were no significant alterations in the mitochondrial membrane potentials of these mutants. We speculate that the shorter life spans of ETC mutants result from multiple mechanisms including the low respiration rate and low energy production rather than just a ROS-dependent path.