Mitochondrial poly (ADP-ribose) polymerase: The Wizard of Oz at work

A Brunyanszki, B Szczesny, L Virág, C Szabo - Free Radical Biology and …, 2016 - Elsevier
Free Radical Biology and Medicine, 2016Elsevier
Among multiple members of the poly (ADP-ribose) polymerase (PARP) family, PARP1
accounts for the majority of PARP activity in mammalian cells. Although PARP1 is
predominantly localized to the nucleus, and its nuclear regulatory roles are most commonly
studied and are the best characterized, several lines of data demonstrate that PARP1 is also
present in the mitochondria, and suggest that mitochondrial PARP (mtPARP) plays an
important role in the regulation of various cellular functions in health and disease. The goal …
Abstract
Among multiple members of the poly(ADP-ribose) polymerase (PARP) family, PARP1 accounts for the majority of PARP activity in mammalian cells. Although PARP1 is predominantly localized to the nucleus, and its nuclear regulatory roles are most commonly studied and are the best characterized, several lines of data demonstrate that PARP1 is also present in the mitochondria, and suggest that mitochondrial PARP (mtPARP) plays an important role in the regulation of various cellular functions in health and disease. The goal of the current article is to review the experimental evidence for the mitochondrial localization of PARP1 and its intra-mitochondrial functions, with focus on cellular bioenergetics, mitochondrial DNA repair and mitochondrial dysfunction. In addition, we also propose a working model for the interaction of mitochondrial and nuclear PARP during oxidant-induced cell death. MtPARP is similar to the Wizard of Oz in the sense that it is enigmatic, it has been elusive for a long time and it remains difficult to be interrogated. mtPARP – at least in some cell types – works incessantly “behind the curtains” as an orchestrator of many important cellular functions.
Elsevier