HIG1 domain family member 1A is a crucial regulator of disorders associated with hypoxia.

Mitochondria play a central role in cellular energy conversion, metabolism, and cell proliferation. The regulation of mitochondrial function by HIGD1A, which is located on the inner membrane of the mitochondria, is essential to maintain cell survival under hypoxic conditions. In recent years, there have been shown other cellular pathways and mechanisms involving HIGD1A diametrically or through its interaction. As a novel regulator, HIGD1A maintains mitochondrial integrity and enhances cell viability under hypoxic conditions, increasing cell resistance to hypoxia. HIGD1A mainly targets cytochrome c oxidase by regulating downstream signaling pathways, which affects the ATP generation system and subsequently alters mitochondrial respiratory function. In addition, HIGD1A plays a dual role in cell survival in distinct degree hypoxia regions of the tumor. Under mild and moderate anoxic areas, HIGD1A acts as a positive regulator to promote cell growth. However, HIGD1A plays a role in inhibiting cell growth but retaining cellular activity under severe anoxic areas. We speculate that HIGD1A engages in tumor recurrence and drug resistance mechanisms. This review will focus on data concerning how HIGD1A regulates cell viability under hypoxic conditions. Therefore, HIGD1A could be a potential therapeutic target for hypoxia-related diseases.

MiR-484 promotes nonalcoholic fatty liver disease progression in mice via downregulation of Sorbs2.

OBJECTIVE: MicroRNA 484 (miR-484) plays a pivotal role in the development and progression of different diseases and is typically described as a mitochondrial regulator. Whether miR-484 is involved in lipid metabolism or exerts a role in nonalcoholic fatty liver disease remains unclear. METHODS: miR-484 levels were examined in the livers of male mice fed a high-fat diet and in hepatocytes treated with free fatty acids. Sorbin and SH3 structural domain-containing protein 2 (Sorbs2) were identified as a novel target of miR-484 by sequencing mRNA in the livers of miR-484 knockout mice. Sorbs2 liver-specific knockdown mice were constructed by tail vein injection of adeno-associated virus vector to miR-484 knockout mice. In addition, genetic manipulation of SORBS2 was performed in human hepatocyte lines, mouse primary hepatocytes, and the liver. RESULTS: Serum and hepatic miR-484 levels are upregulated in nonalcoholic fatty liver disease mice. miR-484 knockdown ameliorated hepatocyte steatosis, whereas miR-484 overexpression increased hepatocyte lipid load. miR-484 knockdown-mediated alleviation of hepatic steatosis, liver injury, inflammation, and apoptosis was compromised after high-fat diet-induced knockdown of Sorbs2 in mouse liver and free fatty acid-induced primary mouse hepatocytes. CONCLUSIONS: These results identify Sorbs2-mediated mitochondrial ß-oxidation and apoptosis that promote miR-484 knockdown-mediated remission of hepatic steatosis.