Intermittent hypoxia training remodels the hepatic mitochondrial network and upregulates ANT expression to enhance hypoxia tolerance in Micropterus salmoides

Oxygen is critical for life, and aquatic organisms are especially susceptible to hypoxic stress caused by environmental fluctuations. However, the mechanisms underpinning their tolerance to hypoxia remain poorly understood. Largemouth bass ( Micropterus salmoides ) is widely distributed across a range of freshwater ecosystems and has significant economic and ecological value. Low oxygen has become a key limiting factor in the aquaculture of this species. This study examined the impact of intermittent hypoxia training (IHT) on hypoxia tolerance of largemouth bass by simulating the daily fluctuations in dissolved oxygen typical of natural aquatic environments. We found that IHT increased the hypoxic tolerance of largemouth bass by activating adenine nucleotide translocase (ANT) which mediated Ca 2+ influx and cellular resistance to hypoxia. Inhibition of ANT compromised hypoxia tolerance by reducing hypoxia-induced mitochondrial Ca 2+ accumulation and mitochondrial quality control. Additionally, ANT inhibition upregulated the expression of genes associated with oxidative stress and apoptosis. These findings highlight a key relationship between ANT and mitochondrial Ca 2+ signaling in response to hypoxia, providing insights into the mechanism that enhances tolerance to hypoxia in largemouth bass. • Intermittent hypoxia training (IHT) stimulated hepatic Ca 2+ influx and mitochondrial quality control. • IHT enhanced tolerance to subsequent hypoxic exposure. • Adenine nucleotide translocase (ANT) enhanced mitochondrial Ca 2+ transport and buffering capacity. • ANT enhanced mitochondrial quality control and antioxidant defenses.