| First Author | Moyzis AG | Year | 2020 |
| Journal | J Mol Cell Cardiol | Volume | 146 |
| Pages | 109-120 | PubMed ID | 32717194 |
| Mgi Jnum | J:338861 | Mgi Id | MGI:6820744 |
| Doi | 10.1016/j.yjmcc.2020.07.009 | Citation | Moyzis AG, et al. (2020) Mcl-1-mediated mitochondrial fission protects against stress but impairs cardiac adaptation to exercise. J Mol Cell Cardiol 146:109-120 |
| abstractText | Myeloid cell leukemia-1 (Mcl-1) is a structurally and functionally unique anti-apoptotic Bcl-2 protein. While elevated levels of Mcl-1 contribute to tumor cell survival and drug resistance, loss of Mcl-1 in cardiac myocytes leads to rapid mitochondrial dysfunction and heart failure development. Although Mcl-1 is an anti-apoptotic protein, previous studies indicate that its functions extend beyond regulating apoptosis. Mcl-1 is localized to both the mitochondrial outer membrane and matrix. Here, we have identified that Mcl-1 in the outer mitochondrial membrane mediates mitochondrial fission, which is independent of its anti-apoptotic function. We demonstrate that Mcl-1 interacts with Drp1 to promote mitochondrial fission in response to various challenges known to perturb mitochondria morphology. Induction of fission by Mcl-1 reduces nutrient deprivation-induced cell death and the protection is independent of its BH3 domain. Finally, cardiac-specific overexpression of Mcl-1OM, but not Mcl-1Matrix, contributes to a shift in the balance towards fission and leads to reduced exercise capacity, suggesting that a pre-existing fragmented mitochondrial network leads to decreased ability to adapt to an acute increase in workload and energy demand. Overall, these findings highlight the importance of Mcl-1 in maintaining mitochondrial health in cells. |
