Loss of major nutrient sensing and signaling pathways suppresses starvation lethality in electron transport chain mutants |
| |
Authors: | Alisha G Lewis Robert Caldwell Jason V Rogers Maria Ingaramo Rebecca Y Wang Ilya Soifer David G Hendrickson R Scott McIsaac David Botstein Patrick A Gibney |
| |
Institution: | University of California, Berkeley;aDepartment of Food Science, Cornell University, Ithaca, NY 14853;bCalico Life Sciences LLC, South San Francisco, CA 94080 |
| |
Abstract: | The electron transport chain (ETC) is a well-studied and highly conserved metabolic pathway that produces ATP through generation of a proton gradient across the inner mitochondrial membrane coupled to oxidative phosphorylation. ETC mutations are associated with a wide array of human disease conditions and to aging-related phenotypes in a number of different organisms. In this study, we sought to better understand the role of the ETC in aging using a yeast model. A panel of ETC mutant strains that fail to survive starvation was used to isolate suppressor mutants that survive. These suppressors tend to fall into major nutrient sensing and signaling pathways, suggesting that the ETC is involved in proper starvation signaling to these pathways in yeast. These suppressors also partially restore ETC-associated gene expression and pH homeostasis defects, though it remains unclear whether these phenotypes directly cause the suppression or are simply effects. This work further highlights the complex cellular network connections between metabolic pathways and signaling events in the cell and their potential roles in aging and age-related diseases. |
| |
Keywords: | |
|
|