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Oxygen is essential for aerobic life, and hypoxia has very severe consequences. Organisms need to overcome low oxygen levels to maintain biological functions during normal development and in disease states. The mechanism underlying the hypoxic response has been widely investigated in model animals such as Drosophila melanogaster and Caenorhabditis elegans. Hypoxia-inducible factor (HIF), a key gene product in the response to oxygen deprivation, is primarily regulated by prolyl hydroxylase domain enzymes (PHDs). However, recent findings have uncovered novel HIF-independent functions of PHDs. This review provides an overview of how invertebrates are able to sustain hypoxic damages, and highlights some recent discoveries in the regulation of cellular signalling by PHDs. Given that some core genes and major pathways are evolutionarily conserved, these research findings could provide insight into oxygen-sensitive signalling in mammals, and have biomedical implications for human diseases.

Regulating the air in low-oxygen environments protects hermetically stored grains from storage pests damage. However, pests that can tolerate hypoxic stress pose a huge challenge in terms of grain storage. We used various biological approaches to determine the fundamental mechanisms of Tribolium castaneum to cope with hypoxia. Our results indicated that limiting the available oxygen to T. castaneum increased glycolysis and inhibited the Krebs cycle, and that accumulated pyruvic acid was preferentially converted to lactic acid via anaerobic metabolism. Mitochondrial aerobic respiration was markedly suppressed for beetles under hypoxia, which also might have led to mitochondrial autophagy. The enzymatic activity of citrate synthase decreased in insects under hypoxia but recovered within 12 h, which suggested that the beetles recovered from the hypoxia. Moreover, hypoxia-reperfusion resulted in severe oxidative damage to insects, and antioxidant levels increased to defend against the high level of reactive oxygen species. In conclusion, our findings show that mitochondria were the main target in T. castaneum in response to low oxygen. The beetles under hypoxia inhibited mitochondrial respiration and increased antioxidant activity after reoxygenation. Our research advances the field of pest control and makes it possible to develop more efficient strategies for hermetic storage.