Disruption of Snf3/Rgt2 glucose sensors decreases lifespan and caloric restriction effectiveness through Mth1/Std1 by adjusting mitochondrial efficiency in yeast

Abstract

Down-regulation of intracellular nutrient signal pathways was proposed to be a primary mechanism of caloric restriction (CR)-mediated lifespan extension. However, the link between lifespan and glucose sensors in the plasma membrane was poorly understood in yeast. Herein, a mutant that lacked glucose sensors (snf3 Delta rgt2 Delta) had impaired glucose fermentation, showed decreased chronological lifespan (CLS), and reduced CLS extension by CR. The mutant also had reduced mitochondrial efficiency, as inferred by increased mitochondrial superoxide and decreased ATP levels. Mth1 and Std1, which are downstream effectors of the Snf3/Rgt2 pathway, were required for viability through mitochondrial function but not fermentative metabolism. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.