Higher Respiratory Activity Decreases Mitochondrial Reactive Oxygen Release and Increases Life Span in Saccharomyces cerevisiae

Mario H Barros,Brian Bandy,Erich B Tahara,Alicia J Kowaltowski

doi:10.1074/jbc.m408918200

Abstract

Increased replicative longevity in Saccharomyces cerevisiae because of calorie restriction has been linked to enhanced mitochondrial respiratory activity. Here we have further investigated how mitochondrial respiration affects yeast life span. We found that calorie restriction by growth in low glucose increased respiration but decreased mitochondrial reactive oxygen species production relative to oxygen consumption. Calorie restriction also enhanced chronological life span. The beneficial effects of calorie restriction on mitochondrial respiration, reactive oxygen species release, and replicative and chronological life span could be mimicked by uncoupling agents such as dinitrophenol. Conversely, chronological life span decreased in cells treated with antimycin (which strongly increases mitochondrial reactive oxygen species generation) or in yeast mutants null for mitochondrial superoxide dismutase (which removes superoxide radicals) and for RTG2 (which participates in retrograde feedback signaling between mitochondria and the nucleus). These results suggest that yeast aging is linked to changes in mitochondrial metabolism and oxidative stress and that mild mitochondrial uncoupling can increase both chronological and replicative life span.

Highlights

The only intervention known to increase average and maximum life span in mammals is caloric restriction (CR),1 a reduction of 25– 60% in calorie intake without essential nutrient deficiency
We measured the release of H2O2, a membrane-permeable reactive oxygen species (ROS), in suspensions of mitochondria isolated from S. cerevisiae grown in YPD containing 2 or 0.5% glucose, a condition previously shown to extend replicative life span [21]
H2O2 release/O2 consumption ratios in yeasts grown in 2% glucose were significantly higher than those of CR mitochondria, indicating that CR alters the quantity of H2O2 generated per O2 consumed

Summary

Introduction

The only intervention known to increase average and maximum life span in mammals is caloric restriction (CR),1 a reduction of 25– 60% in calorie intake without essential nutrient deficiency. The beneficial effects of calorie restriction on mitochondrial respiration, reactive oxygen species release, and replicative and chronological life span could be mimicked by uncoupling agents such as dinitrophenol. These results suggest that yeast aging is linked to changes in mitochondrial metabolism and oxidative stress and that mild mitochondrial uncoupling can increase both chronological and replicative life span.

Results

Conclusion