Calorie Restriction Delays the Aging of Saccharomyces cerevisiae by Improving Complex III Activity via Glutathione Peroxidase 2 (Gpx2)

Abstract

Comparative studies among organisms of different species of the same genus have found that long ‐ lived species contains polymorphisms in the sequence of the cytochrome b (Cyt b) subunit of the complex III leading to lower ROS production, which has been suggested to contribute for longer lifespans. Cyt b is a highly hydrophobic protein that depends on cardiolipin for its function. Cardiolipin peroxidation impairs electron transfer at the cytochrome b and enhances ROS by inducing electron leak. Cardiolipin peroxidation is repaired in mitochondria by Gpx2. Calorie restriction, the only non‐genetic manipulation increasing the lifespan, induces a hormetic response enhancing the activity of antioxidant systems like Gpx. Thus, it is feasible to hypothesize that calorie restriction increases longevity in yeast by preserving complex III activity and electron transfer in the Cyt b in a Gpx2 – dependent manner. Calorie restriction was induced in yeast with 0.05% glucose in YPD medium. YPD 0.05% extended the chronological lifespan of yeast in comparison with YPD medium with standard 2% glucose. Calorie restriction also improved complex III activity in aged yeasts and enhanced the reduction of Cyt b. The beneficial effects of calorie restriction on chronological lifespan, complex III activity and Cyt b reduction were lost in a GPX2Δ yeast mutant. These results suggest that preservation of complex III activity by enhanced electron transfer at Cyt b might be another mechanism by which calorie restriction extends longevity, which might be related with lower ROS generation and protection of cardiolipin against oxidative damage induced by aging.Support or Funding InformationThis work was supported by a grant from Programa de Investigación 2019, Coordinación de la Investigación Científica ‐ UMSNH (CCR).