Mitochondrial PARP1 regulates NAD⁺-dependent poly ADP-ribosylation of mitochondrial nucleoids.

ABSTRACT: PARPs play fundamental roles in multiple DNA damage recognition and repair pathways. Persistent nuclear PARP activation causes cellular NAD⁺ depletion and exacerbates cellular aging. However, very little is known about mitochondrial PARP (mtPARP) and poly ADP-ribosylation (PARylation). The existence of mtPARP is controversial, and the biological roles of mtPARP-induced mitochondrial PARylation are unclear. Here, we demonstrate the presence of PARP1 and PARylation in purified mitochondria. The addition of the PARP1 substrate NAD⁺ to isolated mitochondria induced PARylation, which was suppressed by treatment with the inhibitor olaparib. Mitochondrial PARylation was also evaluated by enzymatic labeling of terminal ADP-ribose (ELTA). To further confirm the presence of mtP

SUBMITTER: Lee JH 

PROVIDER: S-EPMC9794712 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature