Acyl-CoA-binding domain containing 3 modulates NAD+ metabolism through activating poly(ADP-ribose) polymerase 1.

摘要: NAD(+) plays essential roles in cellular energy homoeostasis and redox state, functioning as a cofactor along the glycolysis citric acid cycle pathways. Recent discoveries indicated that, through NAD(+)-consuming enzymes, this molecule may also be involved many other biological outcomes such chromatin remodelling, gene transcription, genomic integrity, cell division, calcium signalling, circadian clock pluripotency. Poly(ADP-ribose) polymerase 1 (PARP1) is an enzyme dysfunctional PARP1 has been linked with onset development of various human diseases, including cancer, aging, traumatic brain injury, atherosclerosis, diabetes inflammation. In present study, we showed that overexpressed acyl-CoA-binding domain containing 3 (ACBD3), Golgi-bound protein, significantly reduced content via enhancing PARP1's activity auto-modification DNA damage-independent manner. We identified extracellular signal-regulated kinase (ERK)1/2 well de novo fatty biosynthesis pathways are ACBD3-mediated activation PARP1. Importantly, oxidative stress-induced greatly attenuated by knocking down ACBD3 gene. Taken together, these findings suggest prominent impacts on metabolism regulating activation-dependent thus function.