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  Mitochondrial NAD + controls nuclear ARTD1-induced ADP-ribosylation

Hopp, A.-K., Teloni, F., Bisceglie, L., Gondrand, C., Raith, F., Nowak, K., et al. (2021). Mitochondrial NAD + controls nuclear ARTD1-induced ADP-ribosylation. Molecular Cell, 81(2), 340-354.e5. doi:10.1016/j.molcel.2020.12.034.

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 Creators:
Hopp, Ann-Katrin, Author
Teloni, Federico, Author
Bisceglie, Lavinia, Author
Gondrand, Corentin1, Author              
Raith, Fabio, Author
Nowak, Kathrin, Author
Muskalla, Lukas, Author
Howald, Anna, Author
Pedrioli, Patrick G.A., Author
Johnsson, Kai1, Author              
Altmeyer, Matthias, Author
Pedrioli, Deena M. Leslie, Author
Hottiger, Michael O., Author
Affiliations:
1Chemical Biology, Max Planck Institute for Medical Research, Max Planck Society, ou_2364732              

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Free keywords: ADP-ribosylation; ARTD1; DNA damage; NAD; PARP inhibitors; PARP-inhibitor; PARP1; mito-nuclear crosstalk; mitochondria; mitochondrial ADP-ribosylation
 Abstract: 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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Language(s): eng - English
 Dates: 2020-10-302020-04-072020-12-182021-01-142021-01-21
 Publication Status: Published in print
 Pages: 21
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
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Title: Molecular Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 81 (2) Sequence Number: - Start / End Page: 340 - 354.e5 Identifier: ISSN: 1097-2765
CoNE: https://pure.mpg.de/cone/journals/resource/954925610929