Pharmacological Inhibition of Poly(ADP-Ribose) Polymerases Improves Fitness and Mitochondrial Function in Skeletal Muscle

E. Pirinen, C. Canto, Y.S. Jo, L. Morato, H. Zhang, K.J. Menzies, E.G. Williams, L. Mouchiroud, N. Moullan, C. Hagberg, W. Li, S. Timmers, R. Imhof, J. Verbeek, A. Pujol, B. van Loon, C. Viscomi, M. Zeviani, P. Schrauwen, A.A. SauveK. Schoonjans, J. Auwerx

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

We previously demonstrated that the deletion of the poly(ADP- (Parp)-1 gene in mice enhances oxidative metabolism, thereby protecting diet-induced obesity. However, the therapeutic use of PARP inhibitors to mitochondrial function remains to be explored. Here, we show tight correlation between Parp-1 expression and energy expenditure in mouse populations, indicating that variations in PARP-1 activity have an on metabolic homeostasis. Notably, these genetic correlations can be into pharmacological applications. Long-term treatment with PARP enhances fitness in mice by increasing the abundance of mitochondrial complexes and boosting mitochondrial respiratory capacity. Furthermore, inhibitors reverse mitochondrial defects in primary myotubes of obese attenuate genetic defects of mitochondrial metabolism in human elegans. Overall, our work validates in worm, mouse, and human models inhibition may be used to treat both genetic and acquired muscle linked to defective mitochondrial function.
Original languageEnglish
Pages (from-to)1034-1041
JournalCell Metabolism
Volume19
Issue number6
DOIs
Publication statusPublished - 1 Jan 2014

Cite this

Pirinen, E., Canto, C., Jo, Y. S., Morato, L., Zhang, H., Menzies, K. J., Williams, E. G., Mouchiroud, L., Moullan, N., Hagberg, C., Li, W., Timmers, S., Imhof, R., Verbeek, J., Pujol, A., van Loon, B., Viscomi, C., Zeviani, M., Schrauwen, P., ... Auwerx, J. (2014). Pharmacological Inhibition of Poly(ADP-Ribose) Polymerases Improves Fitness and Mitochondrial Function in Skeletal Muscle. Cell Metabolism, 19(6), 1034-1041. https://doi.org/10.1016/j.cmet.2014.04.002