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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

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520 |a 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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