Poly(ADP-ribose) polymerase-2 is a lipid-modulated modulator of muscular lipid homeostasis

Judit Márton, Mária Péter, Gábor Balogh, Beáta Bódi, Andras Vida, Magdolna Szántó, Dora Bojcsuk, Laura Jankó, Harjit Pal Bhattoa, Imre Gombos, Karen Uray, Ibolya Horváth, Zsolt Török, Balint L. Balint, Zoltán Papp, László Vígh, Péter Bai

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Abstract

There is a growing body of evidence that poly(ADP-ribose) polymerase-2 (PARP2), although originally described as a DNA repair protein, has a widespread role as a metabolic regulator. We show that the ablation of PARP2 induced characteristic changes in the lipidome. The silencing of PARP2 induced the expression of sterol regulatory element-binding protein-1 and -2 and initiated de novo cholesterol biosynthesis in skeletal muscle. Increased muscular cholesterol was shunted to muscular biosynthesis of dihydrotestosterone, an anabolic steroid. Thus, skeletal muscle fibers in PARP2−/− mice were stronger compared to those of their wild-type littermates. In addition, we detected changes in the dynamics of the cell membrane, suggesting that lipidome changes also affect the biophysical characteristics of the cell membrane. In in silico and wet chemistry studies, we identified lipid species that can decrease the expression of PARP2 and potentially phenocopy the genetic abruption of PARP2, including artificial steroids. In view of these observations, we propose a new role for PARP2 as a lipid-modulated regulator of lipid metabolism.

Original languageEnglish
Pages (from-to)1399-1412
Number of pages14
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1863
Issue number11
DOIs
Publication statusPublished - Nov 2018

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Keywords

  • Androgen
  • Cholesterol
  • Dihydrotestosterone
  • PARP
  • Skeletal muscle

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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