SBK3 suppresses angiotensin II-induced cardiac hypertrophy by regulating mitochondrial metabolism.

Pathological cardiac hypertrophy is one of the risk factors for heart failure, characterized by elevated levels of renin-angiotensin II (Ang II) and catecholamines. SBK3 (SH3 domain binding kinase family member 3), a resident protein in the mitochondria, exhibits relatively high expression selectively in cardiac tissue based on human protein atlas database. Here, we studied the role of SBK3 in Ang II-induced cardiac hypertrophy to identify a new treatment for cardiac hypertrophy and heart failure by targeting mitochondria. The present study, for the first time, reveals the mitochondrial localization of SBK3 in rat cardiomyocytes and demonstrates a decrease in SBK3 protein expression in angiotensin II-perfused mice hearts. We found that maintaining high levels of SBK3 expression both in vivo and in vitro significantly suppressed Ang II-induced cardiac hypertrophy. This is attributed to the fact that overexpression of SBK3 rebalanced the levels of oxidative stress and energy metabolism induced by angiotensin II and inhibited the phosphorylation of dynamin-related protein 1 (Drp1) at the serine 616 site (S616) in cardiomyocytes and mice hearts. These findings suggest that SBK3 is a newly discovered mitochondrial protein capable of suppressing cardiac hypertrophy.