Research Paper Volume 12, Issue 2 pp 1417—1432
SRV2 promotes mitochondrial fission and Mst1-Drp1 signaling in LPS-induced septic cardiomyopathy
- 1 Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fujian Medical University, Fuzhou, Fujian 350001, China
- 2 Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100730, China
received: October 18, 2019 ; accepted: December 24, 2019 ; published: January 17, 2020 ;https://doi.org/10.18632/aging.102691
How to Cite
Copyright © 2020 Shang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Mitochondrial fission is associated with cardiomyocyte death and myocardial depression, and suppressor of ras val-2 (SRV2) is a newly discovered pro-fission protein. In this study, we examined the mechanisms of SRV2-mediated mitochondrial fission in septic cardiomyopathy. Western blotting, ELISA, and immunofluorescence were used to evaluate mitochondrial function, oxidative balance, energy metabolism and caspase-related death, and siRNA and adenoviruses were used to perform loss- and gain-of-function assays. Our results demonstrated that increased SRV2 expression promotes, while SRV2 knockdown attenuates, cardiomyocyte death in LPS-induced septic cardiomyopathy. Mechanistically, SRV2 activation promoted mitochondrial fission and physiological abnormalities by upregulating oxidative injury, ATP depletion, and caspase-9-related apoptosis. Our results also demonstrated that SRV2 promotes mitochondrial fission via a Mst1-Drp1 axis. SRV2 knockdown decreased Mst1 and Drp1 levels, while Mst1 overexpression abolished the mitochondrial protection and cardiomyocyte survival-promoting effects of SRV2 knockdown. SRV2 is thus a key novel promotor of mitochondrial fission and Mst1-Drp1 axis activity in septic cardiomyopathy.