Autophagy Dually Induced by AMP Surplus and Oxidative Stress Enhances Hemocyte Survival and Bactericidal Capacity Via AMPK Pathway in

(Hong Kong oyster) is an ecologically and economically valuable shellfish endemic to South/Southeast Asia. Due to ocean acidification and warming waters, they have become increasingly vulnerable to invading microbes including , a significant foodborne human pathogen. In recent years, outbreaks of have emerged as a perennial phenomenon in parts of the world, necessitating to better understand the biology of host-pathogen interactions in this under-examined marine invertebrate. Although an immunologically relevant autophagy apparatus has been identified in , an evolutionarily close mollusk cousin, the precise mechanistic details of autophagy during infection are still wanting. Here, we compellingly demonstrated that challenge robustly triggered autophagic signaling in hemocytes peaking at 6 h post-infection, which subsequently promoted bacterial clearance and dampened premature apoptosis. Simultaneously, a large surplus of adenosine monophosphate (AMP) and elevations in reactive oxygen species (ROS, specifically mitochondrial O and cellular HO) formation were observed post-infection. Extrinsically applied AMP and ROS could synergistically induce AMP-activated protein kinase (AMPK) phosphorylation to stimulate downstream autophagic events. infection-induced autophagy was pharmacologically shown to be AMPK-dependent . Overall, our results establish autophagy as a crucial arm of host defense against infections in mollusks, and provide new insights into the underappreciated roles of ROS and AMP as co-regulators of autophagy.