Role of Poly (ADP-Ribose) in catalyzing starvation-induced autophagy

Abstract

Poly(ADP-ribosyl)ation (PARylation) is a reversible posttranslational modification of proteins mediated by poly(ADP-ribose) polymerases (PARP proteins, 17 members). Most of the studies developed over the last decades have essentially focused on the biochemical, physiological, and pathological properties of the founding members of the PARP family, PARP-1, PARP-2, and PARP-3. PARylation is carried out by the balance of poly(ADP-ribose) (PAR) synthesis enzymes (PARPs) and PAR decomposing enzymes such as PAR glycohydrolase (PARG) and ADP-ribosyl hydrolase 3 (ARH3). Reversible PARylation is a pleiotropic regulator of various cellular functions (transcription regulation, replication, organization of chromatin domains, genome stability, cell cycle progression, differentiation, and metabolism and cell survival pathways) but uncontrolled PARP activation (overproduction of PAR) may also lead to cell death. PARylation has been implicated in apoptosis, necroptosis, and autophagic cell death (or type II programmed cell death). Macroautophagy (hereafter called autophagy) is an evolutionarily conserved pathway of lysosomes-mediated cellular self-digestion involving the formation of a double-membrane vesicle, the autophagosome, which engulfs cytoplasmic components and delivers them to the lysosomes for degradation. Starvation alarms eukaryotic cells to adjust metabolism to survive. PARP-1 activation is involved in amplifying autophagy by feeding back reactive species of oxygen production/DNA damage/NAD+ consumption axis, leading to AMPK activation/mTORC1 inhibition and subsequently opening autophagy. In the current review we focus on the contribution of PARP and PARylation, as a cellular process involved in cell’s energy homeostasis and posttranslational protein modification, as modulator of autophagy after nutrient deprivation.