Identification of Potential Calorie Restriction-Mimicking Yeast Mutants with Increased Mitochondrial Respiratory Chain and Nitric Oxide Levels

Figure 7

A proposed model for the roles of NO and mitochondrial respiration in CR. In yeast, the cytochrome c oxidase (COX) is likely to be responsible for CR-induced NO production. Under normoxic conditions, CR can activate both oxygen-dependent respiration and nitrite-dependent NO production, and both require the cytochrome c oxidase (COX). CR may increase NO production by derepressing expression of the hypoxic isoform subunits of COX and cytochrome c, which are normally repressed by oxygen. ROS detoxification enzymes protect cells from various ROS-associated damages and are required for certain CR-induced beneficial effects. NO and other mitochondrial ROS may induce adaptive gene expression changes as well as a metabolic shift, which optimize metabolism and improve cellular defense system against the oxidative stress that accumulates with age. For clarity and simplicity, many important longevity factors are not shown. Other pathways may work independently or in concert with mitochondrial respiration and stress response to mediate CR.