Abstract：With the increase of human population density in coastal areas, the anthropogenic input of nutrients and organic matter into coastal waters has resulted in hypoxic events of increasing magnitude, frequency, and duration. Adaptation to hypoxia in cells and tissues leads to the transcriptional induction of a series of genes that participate in erythropoiesis/iron metabolism, angiogenesis, glucose metabolism, cell proliferation/survival and apoptosis. The primary factor mediating this response is the hypoxia-inducible factor-1 (HIF-1): an oxygen-sensitive transcriptional activator. HIF-1 is a dimeric transcriptional complex comprising a HIF-α subunit and a HIF-β (also called the aryl hydrocarbon receptor nuclear translocator, or ARNT) subunit, both of which are members of the basic helix–loop–helix/Per-Arnt-Sim (bHLH/PAS) proteins that are characterized for containing bHLH and PAS conserved domains. They have been recognized primarily for its role in the maintenance of oxygen and energy homoeostasis. The HIF-1α acts as the important regulator of the expression of some genes in response to hypoxia. At the same time, the HIF-1α subunit is O2 labile and is degraded by the proteasome following prolyl-hydroxylation and ubiquitination in normoxic cells. Stability of HIF-1α protein is primarily regulated via an oxygen dependent degradation domain (ODDD) while its transcriptional activity is facilitated via two transactivation domains (N-TAD and C-TAD). These TADs, besides being essential for interaction with transcriptional co-activators such as CBP/p300, are targets for regulation via post-translational modifications such as phosphorylation, acetylation and redox modifications. Under hypoxic conditions, HIF-1α accumulates and forms a heterodimeric DNA-binding complex with HIF-1β, and binds to the hypoxia response element (HRE): 5'-RCGTG-3' on the promoter region of target genes. However, HIF-1β subunit is constitutively expressed in cells. HIF-1β is an obligate dimerization partner for some bHLH-PAS proteins, including AhR (aromatic hydrocarbon receptor): HIF-1α and 2α, and the Sim proteins. The bHLH domain of HIF-1β is mainly responsible for identifying and binding the DNA specific sequence. For PAS domain, it is necessary to form a functional DNA binding complex of HIF-1β and bHLH-PAS family proteins. Although some information is available about the gene expression in response to hypoxia, little is known about the molecular mechanism of the regulation of their expression in aquatic animals. The present review summarized structure and function of HIF-1, O2/PHDs/pVHL degradation pathway of HIF-1, expression regulation, target genes of HIF-1 and it' s research advance in aquatic animals. This article can provide the reference for research on HIF-1 signaling pathways of aquatic animals in the future.
