NAD+ and SIRT3 control microtubule dynamics and reduce susceptibility to antimicrotubule agents
Abstract
Nicotinamide adenine dinucleotide (NAD+) is an endogenous small molecule that has effects on diverse processes, including obesity, lifespan, and cancer. A major goal is to identify the NAD+-regulated cellular pathways that may mediate these effects. In this study, we demonstrate that NAD+ regulates the microtubule cytoskeleton. We find that these effects are mediated by the mitochondrial sirtuin-3. Our findings have implications for many clinically used chemotherapeutics that target microtubules, as we demonstrate that high NAD+ levels can reduce sensitivity to these drugs. These results are also significant because they demonstrate for the first time that NAD+, a molecule regulated by age, diet, and disease state, can influence basic microtubule functions.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- June 2014
- DOI:
- 10.1073/pnas.1404269111
- Bibcode:
- 2014PNAS..111E2443H