Identification of mitochondrial electron transport chain mutations that effect ageing

Abstract

Aging can be defined as the loss of cell functionality by accumulation of deleterious effects. Mitochondrial electron transport chain (ETC) is the main site for reactive oxygen species (ROS) production. According to free radical theory of aging, free radicals produced by normal aerobic respiration accumulate by time and can cause aging. Although previous studies have identified that inner mitochondrial membrane complexes I and III are the major sites of ROS production, role of ETC genes in ROS production is a matter of debate. The purpose of the present study was to determine the ETC mutations that affect aging using S.cerevisiae as a model organism. Deletion mutants of S.cerevisiae lacking 73 genes of ETC were analyzed aging and we found out that nine mutants caused reduction in replicative lifespan. In addition to aging profiles, ROS production levels, respiratory competence and oxidative stress tolerance level of these deletion strains were also investigated. In order to verify lifespan modulation by these genes, they were all overexpressed in wild-type cells and aging profile of these cells was analyzed. Most of the cells lived longer than wild type control cells containing sham vector. Our results suggest that some of the ETC genes play important roles in mitochondrial functions and aging. We hope that our results will contribute to the field of aging studies.