Under the background of global warming, heat stress has become a critical environmental factor limiting aquaculture. Because heat stress is frequently accompanied by hypoxia in aquatic environments, Hypoxia-inducible factor (HIF)—a pivotal transcription factor for maintaining oxygen homeostasis—may play a vital role in heat stress responses. This study identified the core subunits CfHIF-1α and CfARNT in the marine bivalve Chlamys farreri . Structural and phylogenetic analyses demonstrated that both subunits possess conserved bHLH-PAS domains and align with molluscan homologs. CfHIF-1α and CfARNT were ubiquitously expressed during embryonic and larval development, with exceptionally high expression in D -shaped larvae. In adult scallops, they were widely expressed across healthy tissues, particularly in the blood, gill, and mantle. Notably, acute heat stress significantly upregulated CfHIF-1α expression, while CfARNT maintained stable levels. To elucidate the associated regulatory network, genome-wide motif scanning identified 2217 potential downstream target genes containing hypoxia-responsive elements (HREs). These targets were predominantly enriched in genetic information processing and metabolism pathways. To investigate the CfHIF-1α -mediated heat tolerance mechanism, we focused on the key genes CfCAT and CfPSAT1 . RNA interference (RNAi) assays revealed that silencing CfHIF-1α abolished the transcriptional induction of both genes, which subsequently led to reduced catalase (CAT) activity and increased malondialdehyde (MDA) accumulation. These findings demonstrate that CfHIF-1α serves as a central regulator in the heat tolerance of marine bivalves, facilitating redox homeostasis through direct target gene regulation. This research advances our understanding of HIF-1α in heat-hypoxia cross-stress adaptation and elucidates bivalve resilience to ocean warming. • Heat stress significantly upregulates CfHIF-1α expression, whereas CfARNT remains stably expressed in Chlamys farrer. • Genome-wide scanning identified 2217 CfHIF-1α downstream genes involved in genetic information processing and metabolism. • CfHIF-1α activates CfCAT and CfPSAT1 to eliminate ROS and redox balance, enhancing heat stress tolerance in Chlamys farreri .
Li et al. (Wed,) studied this question.