MiR-330-3p suppresses phosphoglycerate mutase family member 5 -inducted mitophagy to alleviate hepatic ischemia-reperfusion injury.

Abstract

Mitochondrial dysfunction plays a central role in hepatic ischemia-reperfusion injury (IRI). The significance of mitophagy in hepatic IRI remains poorly understood. The mechanisms that cause IRI are complex, and many factors are involved in the injury formation process. The miR-330-3p mediates cell proliferation, cell death, and metabolism in various organisms. In this study, the levels of miR-330-3p were significantly downregulated in hepatic IRI, and the number of autophagosomes was increased in response to IRI as obtained under both in vivo and in vitro conditions. These results demonstrate that a reduction in miR-330-3p expression represents an important factor involved with promoting hepatic IRI. Moreover, we found that miR-330-3p interacted with phosphoglycerate mutase family member 5 (PGAM5) to regulate mitophagy. In specific, an overexpression of miR-330-3p diminished PGAM5 levels, which promoted mitophagy in response to IRI. In contrast, a downregulation of miR-330-3p was associated with increased PGAM5 levels leading to increased mitophagy. In conclusion, miR-330-3p suppresses PGAM5-induced mitophagy to alleviate hepatic IRI. Such findings not only reveal some of the mechanistic basis for this microRNA in liver injury, but also provide a foundation for new therapeutic approaches in the treatment of this condition.