Role of PARP-1 in mitochondrial homeostasis

Abstract

Background: Nuclear poly(ADP-ribose) polymerase-1 (PARP-1) is a well characterised protein that accounts for the majority of PARylation reactions using NAD⁺ as a substrate, regulating diverse cellular functions. In addition to its nuclear functions, several recent studies have identified localization of PARP-1 in mitochondria and emphasized its possible role in maintaining mitochondrial homeostasis. Various reports suggest that nuclear PARP-1 has been implicated in diverse mitochondria-specific communication processes.

Scope of review: The present review emphasizes on the potential role of PARP-1 in mitochondrial processes such as bioenergetics, mtDNA maintenance, cell death and mitophagy.

Major conclusions: The origin of mitochondrial PARP-1 is still an enigma; however researchers are trying to establish the cross-talk between nuclear and mitochondrial PARP-1 and how these PARP-1 pools modulate mitochondrial activity.

General significance: A better understanding of the possible role of PARP-1 in mitochondrial homeostasis helps us to explore the potential therapeutic targets to protect mitochondrial dysfunctions.

Keywords: Mitochondrial bioenergetics; Mitochondrial homeostasis; NAD(+) pool; PARP-1; Sirtuins.