Pyridine nucleotide-disulphide oxidoreductase domain 2 (PYROXD2): Role in mitochondrial function.

Pyridine Nucleotide-Disulphide Oxidoreductase Domain 2 (PYROXD2), a Hepatitis B virus X protein (HBx)-interacting protein, is significantly down-regulated in hepatocellular carcinoma (HCC), however its exact biological function remains unclear. The aim of this study is to investigate the subcellular localization and biological function of PYROXD2 in hepatic cells. The results showed that PYROXD2 was imported to the mitochondrial inner membrane/matrix by Tom40 and Tim23, but not Mia40. PYROXD2 151-230aa might be the mitochondrial targeting sequence. PYROXD2 interacted with complex IV subunit COX5B. Knockout of PYROXD2 decreased MMP, intracellular ROS, complex IV activity, cell proliferation, ATP content and mtDNA copy number, but increased mtROS levels and the number of immature mitochondria. In summary, our data illustrated that PYROXD2 localizes to the mitochondrial inner membrane/matrix, and it plays important roles in regulating mitochondrial function.