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Mitochondrial NAD+ Controls Nuclear ARTD1-Induced ADP-Ribosylation.
Hopp, Ann-Katrin; Teloni, Federico; Bisceglie, Lavinia; Gondrand, Corentin; Raith, Fabio; Nowak, Kathrin; Muskalla, Lukas; Howald, Anna; Pedrioli, Patrick G A; Johnsson, Kai; Altmeyer, Matthias; Pedrioli, Deena M Leslie; Hottiger, Michael O.
Affiliation
  • Hopp AK; Department of Molecular Mechanisms of Disease (DMMD), University of Zurich, 8057 Zurich, Switzerland; Life Science Zurich Graduate School, Molecular Life Science Ph.D. Program, University of Zurich, 8057 Zurich, Switzerland.
  • Teloni F; Department of Molecular Mechanisms of Disease (DMMD), University of Zurich, 8057 Zurich, Switzerland; Life Science Zurich Graduate School, Molecular Life Science Ph.D. Program, University of Zurich, 8057 Zurich, Switzerland.
  • Bisceglie L; Department of Molecular Mechanisms of Disease (DMMD), University of Zurich, 8057 Zurich, Switzerland; Life Science Zurich Graduate School, Molecular Life Science Ph.D. Program, University of Zurich, 8057 Zurich, Switzerland.
  • Gondrand C; Department of Chemical Biology, Max Planck Institute for Medical Research, 69120 Heidelberg, Germany.
  • Raith F; Department of Chemical Biology, Max Planck Institute for Medical Research, 69120 Heidelberg, Germany; Faculty of Chemistry and Earth Sciences, University of Heidelberg, 69120 Heidelberg, Germany.
  • Nowak K; Department of Molecular Mechanisms of Disease (DMMD), University of Zurich, 8057 Zurich, Switzerland; Life Science Zurich Graduate School, Molecular Life Science Ph.D. Program, University of Zurich, 8057 Zurich, Switzerland.
  • Muskalla L; Department of Molecular Mechanisms of Disease (DMMD), University of Zurich, 8057 Zurich, Switzerland; Life Science Zurich Graduate School, Cancer Biology Ph.D. Program, University of Zurich, 8057 Zurich.
  • Howald A; Department of Molecular Mechanisms of Disease (DMMD), University of Zurich, 8057 Zurich, Switzerland.
  • Pedrioli PGA; Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland; PHRT-CPAC, ETH Zurich, 8093 Zurich, Switzerland.
  • Johnsson K; Department of Chemical Biology, Max Planck Institute for Medical Research, 69120 Heidelberg, Germany.
  • Altmeyer M; Department of Molecular Mechanisms of Disease (DMMD), University of Zurich, 8057 Zurich, Switzerland.
  • Pedrioli DML; Department of Molecular Mechanisms of Disease (DMMD), University of Zurich, 8057 Zurich, Switzerland.
  • Hottiger MO; Department of Molecular Mechanisms of Disease (DMMD), University of Zurich, 8057 Zurich, Switzerland. Electronic address: michael.hottiger@dmmd.uzh.ch.
Mol Cell ; 81(2): 340-354.e5, 2021 01 21.
Article in En | MEDLINE | ID: mdl-33450210
In addition to its role as an electron transporter, mitochondrial nicotinamide adenine dinucleotide (NAD+) is an important co-factor for enzymatic reactions, including ADP-ribosylation. Although mitochondria harbor the most intra-cellular NAD+, mitochondrial ADP-ribosylation remains poorly understood. Here we provide evidence for mitochondrial ADP-ribosylation, which was identified using various methodologies including immunofluorescence, western blot, and mass spectrometry. We show that mitochondrial ADP-ribosylation reversibly increases in response to respiratory chain inhibition. Conversely, H2O2-induced oxidative stress reciprocally induces nuclear and reduces mitochondrial ADP-ribosylation. Elevated mitochondrial ADP-ribosylation, in turn, dampens H2O2-triggered nuclear ADP-ribosylation and increases MMS-induced ARTD1 chromatin retention. Interestingly, co-treatment of cells with the mitochondrial uncoupler FCCP decreases PARP inhibitor efficacy. Together, our results suggest that mitochondrial ADP-ribosylation is a dynamic cellular process that impacts nuclear ADP-ribosylation and provide evidence for a NAD+-mediated mitochondrial-nuclear crosstalk.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cell Nucleus / Poly (ADP-Ribose) Polymerase-1 / ADP-Ribosylation / Mitochondria / NAD Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Mol Cell Journal subject: BIOLOGIA MOLECULAR Year: 2021 Type: Article Affiliation country: Switzerland

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cell Nucleus / Poly (ADP-Ribose) Polymerase-1 / ADP-Ribosylation / Mitochondria / NAD Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Mol Cell Journal subject: BIOLOGIA MOLECULAR Year: 2021 Type: Article Affiliation country: Switzerland