南方医科大学最新Cell子刊：揭示线粒体VHL蛋白重塑缺氧状态下的细胞代谢

Core Findings - The study confirms that VHL protein is a true regulator of mitochondrial metabolism under hypoxic conditions, rather than merely serving as a "backup adapter" for hypoxia-inducible factors (HIF) in low oxygen environments [5]. Group 1: Research Insights - Under chronic hypoxia, most cytoplasmic VHL protein degrades, while the remaining VHL protein primarily relocates to mitochondria [2] - Mitochondrial VHL binds and inhibits a key component of the leucine metabolism pathway, MCCC2, leading to leucine accumulation and activation of glutamate dehydrogenase, which promotes glutamine hydrolysis to generate sufficient lipids and nucleotides for hypoxic cell growth [2] - SRC-mediated phosphorylation of VHL and PRMT5-mediated methylation of MCCC2 can synergistically regulate the VHL-MCCC2 interaction and its accompanying metabolic reprogramming [2] Group 2: Mechanisms and Implications - The study demonstrates that low oxygen-dependent post-translational modifications regulate the interaction between VHL and MCCC2 [6] - Mitochondrial VHL plays a crucial role in the body's adaptive response to pathological hypoxia [6]