PARP-1在自噬中的作用及其机制研究进展

Role and mechanism of PARP-1 in autophagy:a review of recent studies

聚腺苷二磷酸-核糖聚合酶-1[poly(ADP-ribose)polymerase-1,PARP-1]是PARP酶家族最丰富的亚型。目前对PARP-1的研究主要集中于其在DNA损伤应答、炎症反应和氧化应激等过程的作用,而对PARP-1在自噬中的作用及其机制研究较少。该文综述了PARP-1在自噬中的作用及其机制,发现PARP-1可介导细胞自噬和凋亡之间的双重作用,即PARP-1的适度激活可能通过LKB 1-AMPK-SIRT 1-mTOR-p70S6通路促进细胞自噬,提高细胞存活率;而过度激活会触发PARthanatos,引起细胞凋亡。通过阐明PARP-1在自噬中的作用及其调控自噬的机制,为明确自噬和DNA损伤反应之间的复杂串扰作用提供新见解,并可能在未来对一些疾病的治疗提供新的干预靶点。

Poly(ADP-ribose)polymerase-1(PARP-1)is the most abundant subtype of PARP enzyme family.At present,the study of PARP-1 mainly focuses on its role in DNA damage response,inflammatory response and oxidative stress,while the role of PARP-1 in autophagy and its mechanism are rarely studied.Therefore,by exploring the role of PARP-1 in autophagy and its mechanism,this review found that PARP-1 mediated the dual role between autophagy and apoptosis.Moderate activation of PARP-1 may promote autophagy and improve cell survival through LKB1-AMPK-SIRT 1-mTOR-p70S6 pathway;Overactivation triggers PARthanatos,causing apoptosis.Elucidation of the role of PARP-1 in autophagy and its mechanism of regulating autophagy can provide new insights into the complex cross-talk between autophagy and DNA damage response,and may provide new intervention targets for the treatment of some diseases in the future.