From Cellular Omics to Phenomics: The Role of Sirtuins in the Cellular Stress Response

Lars Tomanek, United States
The cause-and-effect chain of events across biological levels of organization is still an elusive target, challenging the integration of organismal systems. Several thioesters along metabolic pathways, e.g., acetyl-CoA, can interact with proteins to form post-translational modifications (PTMs), i.e., acyl-lysines. These PTMs affect protein function. NAD-dependent deacylases, i.e., sirtuins (SIRTs), can remove these PTMs, shift metabolism and activate an oxidative stress response (OSR), supporting cellular homeostasis during stress. We used a high temporal resolution time course to assess the effects of transcriptomic and proteomic changes on gill tissue and organismal phenotypes in response to heat stress and sirtuin inhibition in the intertidal mussel <i>Mytilus californianus</i>. Using proteomics, inhibitor studies showed that SIRTs affect molecular chaperones, oxidative stress proteins, metabolic enzymes and signaling proteins during heat stress. Additional inhibitor studies showed that food availability and heat stress during acclimation change how SIRTs affect multiple levels of organization: cells (ciliary activity), tissues (particle velocity and respiration rate of gill, siphon opening of mantle) and organismal performance (clearance rate) in <i>M. californianus</i>. Finally, these results are dependent on the circadian rhythm of mussels, in part because SIRT5 levels undergo circadian changes in abundance. The studies were funded by the NSF-grant IOS-1557500 to L. T.