SIRT5 in cancer metabolic reprogramming
Abstract
The sirtuins are a family of NAD+‐dependent protein deacylases that regulate metabolism and other diverse aspects of cell biology. Three sirtuins (SIRT3, SIRT4, and SIRT5) are present in the mitochondrial matrix. SIRT5 is an inefficient deacetylase, instead removing succinyl, malonyl, and glutaryl groups from lysines of its target proteins. To provide insight into SIRT5 functions, together with Dr. Yingming Zhao's group, we previously carried out proteomics profiling of the cellular succinylome (Park et al., Mol. Cell 2013). This revealed potential impacts of succinylation on enzymes involved in diverse aspects of mitochondrial metabolism. We tested the impact of SIRT5 on two substrates identified in our studies, Pyruvate Dehydrogenase Complex (PDC) and Succinate Dehydrogenase (SDH). SIRT5 inhibited biochemical activities of both complexes, and suppressed overall mitochondrial respiration in the presence of glucose, pyruvate, and succinate.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2016
- Source ID
- 10.1096/fasebj.30.1_supplement.439.3
Entities
People
- David B. Lombard
- Jeongsoon Park
- Surinder Kumar
Organizations
- Glenn Foundation for Medical Research
- National Institutes of Health
- United States Department of Defense
- University of Michigan