Succinate induces aberrant mitochondrial fission in cardiomyocytes through GPR91 signaling

• DOI: 10.1038/s41419-018-0708-5
• Publication Date: 2018-06-04T08:40:43Z
• Authors: Yi-Tong Lu; Lan-Zhu Li; Yi-Lin Yang; Xiaojian Yin; Qun Liu; Lei Zhang; Kang Liu; Baolin Liu; Jia Li; Lian-Wen Qi
• Keywords: Dynamins; Male; 0301 basic medicine; Mice, Inbred ICR; Isoproterenol; Myocardial Ischemia; Apoptosis; Mitochondrial Dynamics; Models, Biological; Article; Mitochondria; Rats; Enzyme Activation; Mitochondrial Proteins; Oxygen; Protein Kinase C-delta; 03 medical and health sciences; Glucose; Animals, Newborn; Animals; Myocytes, Cardiac; Amino Acid Sequence; Extracellular Signal-Regulated MAP Kinases

Abstract Altered mitochondrial metabolism acts as an initial cause for cardiovascular diseases and metabolic intermediate succinate emerges a mediator of dysfunction. This work aims to investigate whether or not extracellular accumulation its targeted G protein-coupled receptor-91 (GPR91) activation induce cardiac injury through impairment. The results showed that promoted the translocation dynamin-related protein 1 (Drp1) mitochondria via kinase Cδ (PKCδ) activation, induced fission factor (MFF) phosphorylation signal-regulated kinases-1/2 (ERK1/2) in GPR91-dependent manner. As result, enhanced localization MFF Drp1 fission, leading dysfunction cardiomyocyte apoptosis. We further inhibition release GPR91 signaling ameliorated oxygen–glucose deprivation-induced cardiomyocytes isoproterenol-induced myocardial ischemia mice. Taken together, these response ischemia, activated regulation PKCδ ERK1/2 branches. These findings suggest succinate-mediated might be potential therapeutic strategy protecting from ischemic injury.