Poly(ADP-ribose) polymerases as modulators of mitochondrial activity

• Activation of poly(ADP-ribose) polymerases-1 and -2 (PARP-1 and PARP-2) deteriorates mitochondrial activity.
• NAD+ and ATP degradation are not coupled to each other upon PARP activation.
• PARPs interact with transcription factors modulating mitochondrial activity.
• PARPs can be positive regulators of mitochondrial output under sublethal stress.
• PARP inhibition is an attractive target for treating mitochondrial dysfunction.

Mitochondria are essential in cellular stress responses. Mitochondrial output to environmental stress is a major factor in metabolic adaptation and is regulated by a complex network of energy and nutrient sensing proteins. Activation of poly(ADP-ribose) polymerases (PARPs) has been known to impair mitochondrial function; however, our view of PARP-mediated mitochondrial dysfunction and injury has only recently fundamentally evolved. In this review, we examine our current understanding of PARP-elicited mitochondrial damage, PARP-mediated signal transduction pathways, transcription factors that interact with PARPs and govern mitochondrial biogenesis, as well as mitochondrial diseases that are mediated by PARPs. With PARP activation emerging as a common underlying mechanism in numerous pathologies, a better understanding the role of various PARPs in mitochondrial regulation may help open new therapeutic avenues.