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Mitochondrial NAD+ controls nuclear ARTD1-induced ADP-ribosylation

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 under...

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Hauptverfasser: Hopp, Ann-Katrin (VerfasserIn) , Teloni, Federico (VerfasserIn) , Bisceglie, Lavinia (VerfasserIn) , Gondrand, Corentin (VerfasserIn) , Raith, Fabio (VerfasserIn) , Nowak, Kathrin (VerfasserIn) , Muskalla, Lukas (VerfasserIn) , Howald, Anna (VerfasserIn) , Pedrioli, Patrick G. A. (VerfasserIn) , Johnsson, Kai (VerfasserIn) , Altmeyer, Matthias O. (VerfasserIn) , Pedrioli, Deena M. Leslie (VerfasserIn) , Hottiger, Michael (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 14 January 2021
In: Molecular cell
Year: 2021, Jahrgang: 81, Heft: 2, Pages: 340-354,e1-e5
ISSN:1097-4164
DOI:10.1016/j.molcel.2020.12.034
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.molcel.2020.12.034
Verlag, lizenzpflichtig, Volltext: https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=DynamicDOIArticle&SrcApp=WOS&KeyAID=10.1016%2Fj.molcel.2020.12.034&DestApp=DOI&SrcAppSID=C4JHXkMJnLnlNTB6bMU&SrcJTitle=MOLECULAR+CELL&DestDOIRegistrantName=Elsevier
Volltext
Verfasserangaben:Ann-Katrin Hopp, Federico Teloni, Lavinia Bisceglie, Corentin Gondrand, Fabio Raith, Kathrin Nowak, Lukas Muskalla, Anna Howald, Patrick G.A. Pedrioli, Kai Johnsson, Matthias Altmeyer, Deena M. Leslie Pedrioli, Michael O. Hottiger
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 09.09.2021
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Beschreibung:Online Resource
ISSN:1097-4164
DOI:10.1016/j.molcel.2020.12.034

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