PARP10 (ARTD10) modulates mitochondrial function

PLoS One. 2018 Jan 2;13(1):e0187789. doi: 10.1371/journal.pone.0187789. eCollection 2018.

Abstract

Poly(ADP-ribose) polymerase (PARP)10 is a PARP family member that performs mono-ADP-ribosylation of target proteins. Recent studies have linked PARP10 to metabolic processes and metabolic regulators that prompted us to assess whether PARP10 influences mitochondrial oxidative metabolism. The depletion of PARP10 by specific shRNAs increased mitochondrial oxidative capacity in cellular models of breast, cervical, colorectal and exocrine pancreas cancer. Upon silencing of PARP10, mitochondrial superoxide production decreased in line with increased expression of antioxidant genes pointing out lower oxidative stress upon PARP10 silencing. Improved mitochondrial oxidative capacity coincided with increased AMPK activation. The silencing of PARP10 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 PARP10 expression increases survival in gastric cancer. Furthermore, PARP10 expression decreased upon fasting, a condition that is characterized by increases in mitochondrial biogenesis. Finally, lower PARP10 expression is associated with increased fatty acid oxidation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylate Kinase / metabolism
  • Animals
  • Blotting, Western
  • Cell Line
  • Cell Proliferation / physiology
  • Electrophoresis, Polyacrylamide Gel
  • Gene Silencing
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Mitochondria / physiology*
  • Oxidation-Reduction
  • Oxidative Stress
  • Oxygen Consumption
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Proto-Oncogene Proteins
  • PARP10 protein, human
  • Poly(ADP-ribose) Polymerases
  • Adenylate Kinase

Grants and funding

Our work was funded by grants from NKFIH (K108308, K123975, KKP126710, GINOP-2.3.3-15-2016-00021, GINOP-2.3.2-15-2016-00006), the Momentum fellowship of the Hungarian Academy of Sciences and a Campus France fellowship to PB, and the German Science Foundation (DFG LU 466/16-1) to BL. PB was also financed by the University of Debrecen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.