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Although HIF-1Ξ± does not stabilize mitochondrial function by promoting the transcription of mitochondrial DNA as SIRT3 does (Wang et al., 2022), HIF-1Ξ±, as a protein regulating iron homeostasis, decreases the partial pressure of oxygen, translocates to the mitochondria, and acts directly on the mitochondrial respiratory chain complex in hypoxia, thereby blocking the sustained effects of mitochondrial ROS on mitochondrial function and ultimately achieving multi-modal neuroprotection (FouchΓ© et al., 2023)
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