Deficiency of PvDRAM2 increased the nitrite sensitivity of Pacific white shrimp (Penaeus vannamei) by inhibiting autophagy

Comp Biochem Physiol C Toxicol Pharmacol. 2024 Nov 4:110068. doi: 10.1016/j.cbpc.2024.110068. Online ahead of print.

Abstract

Autophagy is an essential response mechanism to environmental stress during the evolution of organisms. DRAM2 (Damage-regulated autophagy regulator 2) is recognized as necessary for the process of p53-mediated cell apoptosis. Although the role of DRAM2 in apoptosis has been confirmed, the mechanism of its relationship with autophagy is still unclear. Here we describe PvDRAM2 features and functions. We found that nitrite stress induced autophagy accumulation and ROS production. A novel DRAM-homologous protein, DRAM2, was cloned, and its expression is significantly up-regulated under nitrite stress conditions. PvDRAM2 primarily localizes within the cytoplasmic lysosome.Loss of PvDRAM2 increased sensitivity response to nitrite stress of Pacific white shrimp. And silenced of PvDRAM2 promoted ROS production and inhibited autophagy accumulation. In addition, silenced of PvDRAM2 decreased the autophagy-related protein of p62, Beclin 1, and LC3 expression under nitrite stress of Pacific white shrimp. Collectively, these studies uncover a novel critical role for PvDRAM2 in regulating autophagy under nitrite stress. Specifically, PvDRAM2 is essential for the induction of autophagy, enabling Pacific white shrimp to adapt to environmental stress. This provides mechanistic insight into how autophagy functions as a way for Pacific white shrimp to cope with environmental challenges.

Keywords: Autophagy; DRAM2; Nitrite; Penaeus vannamei; ROS.