Heat-induced longevity in budding yeast requires respiratory metabolism and glutathione recycling

Abstract

Heat-induced hormesis is a well-known conserved phenomenon in aging, traditionally attributed to the benefits conferred by increased amounts of heat shock (HS) proteins. Here we find that the key event for the HS-induced lifespan extension in budding yeast is the switch from glycolysis to respiratory metabolism. The resulting increase in reactive oxygen species activates the antioxidant response, supported by the redirection of glucose from glycolysis to the pentose phosphate pathway, increasing the production of NADPH. This sequence of events culminates in replicative lifespan (RLS) extension, implying decreased mortality per generation that persists even after the HS has finished. We found that switching to respiratory metabolism, and particularly the consequent increase in glutathione levels, were essential for the observed RLS extension. These results draw the focus away solely from the HS response and demonstrate that the antioxidant response has a key role in heat-induced hormesis. Our findings underscore the importance of the changes in cellular metabolic activity for heat-induced longevity in budding yeast.

Oxidative Stress in Neurodegenerative Diseases: From a Mitochondrial Point of View

“…Interestingly, a switch from glycolysis to respiratory metabolism in yeast has been found to increase ROS production, activate the antioxidant response, and increase NADPH production, causing lifespan extension and hormesis response [48].…”

Cytoplasmic and Mitochondrial NADPH-Coupled Redox Systems in the Regulation of Aging

“…Since deletion of NADPH-generating enzymes in yeast generally led to increased longevity, a lifespan-extending signaling pathway appears to be activated by increased NADP + /NADPH. Other studies in yeast have shown that the heat shock-induced increase in replicative longevity was due to a transient increase in superoxide levels that signaled for the redirection of metabolic flux from glycolysis to the PPP to increase NADPH synthesis and GSH levels [197].…”

The first Autumn School on Proteostasis: from molecular mechanisms to organismal consequences

“…Moreover, proteostasis and metabolism are known to interact through pleiotropic mechanisms mediated by TORC1 and Hsp90 (Gopinath and Leu 2016;Perić et al 2017). Taken together, Dr. Krisko's work suggests that global metabolic reprogramming is required to achieve lifespan extension in yeast (Musa et al 2018).…”