Overexpression of PaParp encoding the poly(ADP-ribose) polymerase of Podospora anserina affects organismal aging

Abstract

Poly(ADP-ribose) polymerases (PARPs) are a diverse group of proteins present in all multicellular eukaryotes. They catalyze the NAD(+)-dependent modification of proteins with poly(ADP-ribose). Poly(ADP-ribosyl)ation plays a key role in a plethora of processes including DNA repair, tumor progression and aging. Here we report that PaPARP, the single protein with a PARP catalytic domain, in the fungal aging model Podospora anserina, indeed displays a NAD(+)-dependent poly(ADP-ribose) polymerase activity. While unable to select a PaParp deletion strain, we succeeded in the generation of PaParp overexpressors. Biochemically these strains are characterized by reduced mitochondrial membrane potential and a lowered ATP content. They show an increased sensitivity against different stressors including the DNA damaging agent phleomycin, the reactive oxygen generator paraquat, and the apoptosis inducer farnesol. PaParp overexpressors are impaired in growth, in pigmentation and fertility, and have a shortened lifespan. Our results demonstrate the relevance of poly(ADP-ribose) metabolism for aging and development in P. anserina. With a single PARP this metabolism is less complex than in higher eukaryotes and thus P. anserina appears to be a promising system to connect basic PARP functions with the well established network of pathways relevant for organismal aging.