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Mitochondrial NAD+ Controls Nuclear ARTD1-Induced ADP-Ribosylation.
- Source :
-
Molecular Cell . Jan2021, Vol. 81 Issue 2, p340-340. 1p. - Publication Year :
- 2021
-
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, H 2 O 2 -induced oxidative stress reciprocally induces nuclear and reduces mitochondrial ADP-ribosylation. Elevated mitochondrial ADP-ribosylation, in turn, dampens H 2 O 2 -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. • Mitochondrial ADP-ribosylation was identified by different methods • Mitochondrial ADP-ribosylation reversibly increased after respiratory chain inhibition • H 2 O 2 treatment induces nuclear and reduces mitochondrial ADP-ribosylation • Elevated mitochondrial ADP-ribosylation dampened MMS-induced ARTD1 chromatin retention Hopp et al. detect mitochondrial ADP-ribosylation and characterize its dependency on intracellular NAD+ homeostasis. While respiratory chain inhibition increases mitochondrial ADP-ribosylation, hydrogen peroxide treatment reduces mitochondrial ADP-ribosylation and reciprocally induces nuclear ADP-ribosylation. This dynamic and reversable process is dependent on a NAD+-dependent mitochondrial-nuclear crosstalk. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10972765
- Volume :
- 81
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Molecular Cell
- Publication Type :
- Academic Journal
- Accession number :
- 148122779
- Full Text :
- https://doi.org/10.1016/j.molcel.2020.12.034