Molecular Mechanisms of FUNDC1 and Its Interacting Proteins in Regulating Hypoxia-Induced Mitophagy and Ferroptosis in Macrobrachium nipponense
Macrobrachium nipponense is one of the most important freshwater economic shrimp species cultured in the Yangtze River Delta of China, with a wide farming distribution and high production yield. However, this species is highly sensitive to hypoxic stress. In aquaculture practice, a decrease in dissolved oxygen in the water can weaken feeding capacity, reduce vitality, and induce surfacing behavior, and in severe cases may even lead to large-scale mortality, thereby causing considerable economic losses. Mitochondrial quality control plays an important role in maintaining cellular adaptation to hypoxic environments. Among these regulatory processes, mitophagy selectively removes damaged mitochondria and is essential for maintaining mitochondrial function and cellular energy supply, whereas ferroptosis is a form of programmed cell death characterized by the abnormal accumulation of iron-dependent lipid peroxides. Previous studies have shown that FUN14 domain-containing protein 1 (FUNDC1), an important receptor protein located on the outer mitochondrial membrane, plays a key role in hypoxia-induced mitophagy. Phosphoglycerate mutase 5 (PGAM5) is also involved in mitochondrial homeostasis and hypoxic response, and can regulate mitophagy activity by modulating the phosphorylation state of FUNDC1. However, the molecular mechanisms of PGAM5 and FUNDC1 in the hypoxia response of M. nipponense remain unclear. Therefore, this study focused on the roles of FUNDC1 and its interacting proteins in hypoxia-induced mitophagy and ferroptosis in M. nipponense. The main results are as follows.