E3 Ubiquitin Ligase TRIM9 Ubiquitin Modified-Beclin1 Regulates Autophagy to Relieve Myocardial Ischemia Reperfusion Injury

TRI partite motif (TRIM) family proteins are RING finger domain-containing proteins, which are related with the maintenance of cellular functions. TRIM9, a pivotal E3 ubiquitin ligase, has been implicated in the pathogenesis of many diseases. However, the role of TRIM9 in myocardial ischemia-reperfusion injury (MIRI) remains unknown. In this study, we found that TRIM9 expression is up-regulated in MIRI in vivo and in vitro model. The inhibition of TRIM9 expression further increased the protein levels of LC3II and p62, while they were elevated in the process of MIRI, suggesting the disruption of autophagic flow. Mechanistically, TRIM9 down-regulated the expression of Beclin1, a crucial protein in autophagy, and promoted the ubiquitination of Beclin1, followed by the decreased expression of LC3II and p62. Collectively, our data revealed that TRIM9 can protect against MIRI and might be a novel and potential therapeutic target for cardiovascular disease.