PARP10 (ARTD10) modulates mitochondrial function.

Poly(ADP-ribose) polymerase is a family member that performs mono-ADP-ribosylation of target proteins. Recent studies have linked to metabolic processes and metabolic regulators that prompted us to assess whether Pduanyu3710 influences mitochondrial oxidative metabolism. The depletion of Pduanyu3710 by specific shRNAs increased mitochondrial oxidative capacity in cellular models of breast, cervical, colorectal and exocrine pancreas cancer. Upon silencing of mitochondrial superoxide production decreased in line with increased expression of antioxidant genes pointing out lower oxidative stress upon Pduanyu3710 silencing. Improved mitochondrial oxidative capacity coincided with increased AMPK activation. The silencing of Pduanyu3710 in MCF7 and CaCo2 cells decreased the proliferation rate that correlated with increased expression of anti-Warburg enzymes (Foxo1, PGC-1α, IDH2 and fumarase). By analyzing an online database we showed that lower Pduanyu3710 expression increases survival in gastric cancer. Furthermore, Pduanyu3710 expression decreased upon fasting, a condition that is characterized by increases in mitochondrial biogenesis. Finally, lower Pduanyu3710 expression is associated with increased fatty acid oxidation.

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