Open AccessPARP10 (ARTD10) modulates mitochondrial function
Author(s) -
János Marton,
Tamás Fodor,
L Nagy,
András Vida,
Gréta Kis,
Attila Brunyánszki,
Miklós Antal,
Bernhard Lüscher,
Péter Bai
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0187789
Subject(s) - mitochondrial biogenesis , sirt3 , mitochondrion , oxidative stress , gene silencing , oxidative phosphorylation , biology , poly adp ribose polymerase , microbiology and biotechnology , mitochondrial ros , chemistry , biochemistry , enzyme , nad+ kinase , sirtuin , polymerase , gene
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.