Impacts of N-glycanase1 (NGLY1) Down Regulation on the Function of Mitochondria

N-glycanase 1 (NGLY1) is involved in intracellular misfolded protein degradation, releasing a de-N-glycosylated protein and a complete N-oligosaccharide. Enzymatic defects in NGLY1 may cause NGLY1-related congenital disorder of deglycosylation (NGLY1-CDDG). NGLY1 patients exhibit cognition and coordination defects, and the regulatory impact of NGLY1 in the organism deserves in-depth investigation. In this study, we established NGLY1-knockdown human foreskin fibroblasts-1 (HFF-1) cells and observed mitochondrial function impairments. We conservatively suggest that NGLY1 has global regulatory roles within cells. The Calnexin/IP3R/VDAC1 axis acts as a communication bridge and represents one mechanism underlying NGLY1-mediated modulation of mitochondrial function. This has significant implications for addressing the clinical disease problems presented by NGLY1-CDDG.