1. Mitochondrial NAD + Controls Nuclear ARTD1-Induced ADP-Ribosylation.
- Author
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Hopp AK, Teloni F, Bisceglie L, Gondrand C, Raith F, Nowak K, Muskalla L, Howald A, Pedrioli PGA, Johnsson K, Altmeyer M, Pedrioli DML, and Hottiger MO
- Subjects
- Animals, Antimycin A analogs & derivatives, Antimycin A pharmacology, Cell Line, Cell Line, Tumor, Cell Nucleus drug effects, Cell Nucleus genetics, Chromatin chemistry, Chromatin metabolism, Electron Transport drug effects, HeLa Cells, Humans, Hydrogen Peroxide pharmacology, Methacrylates pharmacology, Mice, Mice, Inbred C57BL, Mitochondria drug effects, Mitochondria genetics, Myoblasts cytology, Myoblasts drug effects, Myoblasts enzymology, Oligomycins pharmacology, Osteoblasts cytology, Osteoblasts drug effects, Osteoblasts enzymology, Poly (ADP-Ribose) Polymerase-1 genetics, Rotenone pharmacology, Thiazoles pharmacology, ADP-Ribosylation drug effects, Cell Nucleus enzymology, Mitochondria enzymology, NAD metabolism, Poly (ADP-Ribose) Polymerase-1 metabolism
- 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, H2 O2 -induced oxidative stress reciprocally induces nuclear and reduces mitochondrial ADP-ribosylation. Elevated mitochondrial ADP-ribosylation, in turn, dampens H2 O2 -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., Competing Interests: Declaration of Interests The authors declare no financial interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
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