Title: Pharmacological Inhibition of Poly(ADP-Ribose) Polymerases Improves Fitness and Mitochondrial Function in Skeletal Muscle
Authors: Pirinen, Eija ×
Cantó, Carles
Jo, Young Suk
Morato, Laia
Zhang, Hongbo
Menzies, Keir J
Williams, Evan G
Mouchiroud, Laurent
Moullan, Norman
Hagberg, Carolina
Li, Wei
Timmers, Silvie
Imhof, Ralph
Verbeek, Jef
Pujol, Aurora
van Loon, Barbara
Viscomi, Carlo
Zeviani, Massimo
Schrauwen, Patrick
Sauve, Anthony A
Schoonjans, Kristina
Auwerx, Johan #
Issue Date: Jun-2014
Publisher: Cell Press
Series Title: Cell Metabolism vol:19 issue:6 pages:1034-41
Article number: S1550-4131(14)00165-X
Abstract: We previously demonstrated that the deletion of the poly(ADP-ribose)polymerase (Parp)-1 gene in mice enhances oxidative metabolism, thereby protecting against diet-induced obesity. However, the therapeutic use of PARP inhibitors to enhance mitochondrial function remains to be explored. Here, we show tight negative correlation between Parp-1 expression and energy expenditure in heterogeneous mouse populations, indicating that variations in PARP-1 activity have an impact on metabolic homeostasis. Notably, these genetic correlations can be translated into pharmacological applications. Long-term treatment with PARP inhibitors enhances fitness in mice by increasing the abundance of mitochondrial respiratory complexes and boosting mitochondrial respiratory capacity. Furthermore, PARP inhibitors reverse mitochondrial defects in primary myotubes of obese humans and attenuate genetic defects of mitochondrial metabolism in human fibroblasts and C. elegans. Overall, our work validates in worm, mouse, and human models that PARP inhibition may be used to treat both genetic and acquired muscle dysfunction linked to defective mitochondrial function.
ISSN: 1550-4131
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Hepatology
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science