Mitochondria and lifespan of budding yeast

Mitochondria play a crucial role in eukaryotic cells. The mitochondrial electron transport chain (ETC) generates adenosine triphosphate (ATP), which serves as an energy source for numerous critical cellular activities. However, the ETC also generates deleterious reactive oxygen species (ROS) as a natural byproduct. Caloric restriction (CR) has been shown to extend lifespan and prevent cellular senescence in various species ranging from yeast to humans. We analyzed the chronological lifespan (CLS), growth phenotype, mitochondrial membrane potential (MMP), and intracellular ATP and mitochondrial superoxide level of 33 single ETC component deleted strains during the chronological aging process under non-restricted (NR) and CR conditions. Among the ETC mutant strains, 14 showed a significantly shorter CLS under NR. These short-lived strains showed higher superoxide levels and lower ATP levels without alteration of MMP. Interestingly, defects in 17 of these 33 ETC gene deleted strains showed loss of both respiratory function and CR-induced CLS extension. On the contrary, the other 16 respiration-capable mutants showed increased CLS upon CR along with increased MMP and intracellular ATP levels, with decreased mitochondrial superoxide generation. In summary, ETC mutations decreased the lifespan of yeast due to impaired mitochondrial efficiency and respiration is essential for lifespan extension by CR.