| First Author | Escudero S | Year | 2018 |
| Journal | Mol Cell | Volume | 69 |
| Issue | 5 | Pages | 729-743.e7 |
| PubMed ID | 29499131 | Mgi Jnum | J:260806 |
| Mgi Id | MGI:6150129 | Doi | 10.1016/j.molcel.2018.02.005 |
| Citation | Escudero S, et al. (2018) Dynamic Regulation of Long-Chain Fatty Acid Oxidation by a Noncanonical Interaction between the MCL-1 BH3 Helix and VLCAD. Mol Cell 69(5):729-743.e7 |
| abstractText | MCL-1 is a BCL-2 family protein implicated in the development and chemoresistance of human cancer. Unlike its anti-apoptotic homologs, Mcl-1 deletion has profound physiologic consequences, indicative of a broader role in homeostasis. We report that the BCL-2 homology 3 (BH3) alpha helix of MCL-1 can directly engage very long-chain acyl-CoA dehydrogenase (VLCAD), a key enzyme of the mitochondrial fatty acid beta-oxidation (FAO) pathway. Proteomic analysis confirmed that the mitochondrial matrix isoform of MCL-1 (MCL-1(Matrix)) interacts with VLCAD. Mcl-1 deletion, or eliminating MCL-1(Matrix) alone, selectively deregulated long-chain FAO, causing increased flux through the pathway in response to nutrient deprivation. Transient elevation in MCL-1 upon serum withdrawal, a striking increase in MCL-1 BH3/VLCAD interaction upon palmitic acid titration, and direct modulation of enzymatic activity by the MCL-1 BH3 alpha helix are consistent with dynamic regulation. Thus, the MCL-1 BH3 interaction with VLCAD revealed a separable, gain-of-function role for MCL-1 in the regulation of lipid metabolism. |
