Med Gas Res. 2026 Jun 01. 16(2): 116-124
JOURNAL/mgres/04.03/01612956-202606000-00006/figure1/v/2025-08-18T154854Z/r/image-tiff Although mitochondria and related proteins are essential for mitochondrial preservation, the functions of some of these proteins remain unknown. The novel protein oxidoreductase-like domain containing 1 (OXLD1/C17orf90, UniProtKB Q5BKU9) have attracted our attention because of its correlation with mitochondria. This study revealed a decrease in OXLD1 levels in cardiomyocytes cultured in 1% oxygen for 24 hours. Suppressing OXLD1 increases mitochondrial injury under both normoxic and hypoxic conditions. This is evidenced by decreased mitochondrial membrane potential and increased reactive oxygen species production. Meanwhile, suppressing OXLD1 decreased mitochondrial oxidative phosphorylation. Overexpression of OXLD1 decreased mitochondrial injury under normoxia and hypoxia, as indicated by an increase in the mitochondrial membrane potential and a decrease in reactive oxygen species production. Moreover, overexpression of OXLD1 enhanced mitochondrial oxidative phosphorylation. Additionally, we found that OXLD1 regulates mitochondrial oxidative phosphorylation by affecting mitochondrial complexes I and V. OXLD1 plays a crucial role in protecting cardiomyocytes by improving mitochondrial function under low-oxygen conditions. OXLD1 achieves this protection through interactions with mitochondrial complexes I and V. Therefore, OXLD1 may serve as a new and important regulator of mitochondrial function.
Keywords: C17orf90; MMP; OXLD1; ROS; cardiomyocytes; hypoxia; mitochondria; mitochondrial complex I; mitochondrial complex V; oxidative phosphorylation