Mitochondrial NAD+ Controls Nuclear ARTD1-Induced ADP-Ribosylation.
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.
Key words
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