Mitochondria are important for energy production and cardiomyocyte homeostasis. OMA1, a metalloendopeptidase, initiates the proteolytic process of the fusion-allowing protein OPA1, to deteriorate mitochondrial structure and function. In this study, mouse embryonic fibroblasts (MEFs) and neonatal mouse cardiomyocytes (NMCMs) subjected to hypoxia-reperfusion injury (HRI) and/or H2O2 were used to mimic oxidative stress in the heart following ischemia-reperfusion injury (IRI). In vitro experiments demonstrated that HRI or stimulation with H2O2 induced self-cleavage of OMA1 and the subsequent conversion of OPA1 from its long form to its short form, leading to mitochondrial fragmentation, cytochrome c release and apoptosis. By using Molecular Operating Environment (MOE) software to simulate the binding interaction of 2295 phytochemicals against OMA1, epigallocatechin gallate (EGCG) and betanin were selected as candidates of OMA1 inhibitor. We found that EGCG directly interacted with OMA1 and potently inhibited self-cleavage of OMA1, leading to attenuated OPA1 cleavage. This study, therefore, suggests to use OMA1 inhibition induced by EGCG to treat cardiac IRI.
Keywords: EGCG; Ischemia-reperfusion injury; Mitochondrial dynamics; OMA1; OPA1.
© 2019. Published by The Company of Biologists Ltd.