代谢重编程对支持癌细胞生长和运动以及决定细胞命运至关重要。线粒体蛋白醋酸化调节线粒体代谢，与癌细胞的迁移和侵袭有关。线粒体蛋白醋酸化在癌细胞迁移中的功能角色仍不清楚。作为线粒体蛋白醋酸化调节因子，广泛的氨基酸合成控制5样蛋白（GCN5L1）在小鼠肝脏中功能于代谢重编程。我们发现在转移性肝癌组织中GCN5L1的表达显著下降。GCN5L1的丧失通过增强脂肪酸氧化导致反应性氧化物（ROS）生成，随后激活细胞ERK和DRP1以促进线粒体分裂和上皮细胞向间质化转化（EMT）以促进细胞迁移。此外，棕榈酸和肉碱刺激的脂肪酸氧化促进线粒体分裂和EMT基因表达以激活HCC细胞迁移。另一方面，增加的细胞乙酰辅酶A水平，是脂肪酸氧化的产物，增强了HCC细胞的迁移。总之，我们的研究揭示了GCN5L1在HCC中的转移抑制剂作用和其潜在机制，并提供了FAO逆行控制HCC转移的证据。 ©2023年。作者，独家授权施普林格自然有限公司。

Metabolic reprogram is crucial to support cancer cell growth and movement as well as determine cell fate. Mitochondrial protein acetylation regulates mitochondrial metabolism, which is relevant to cancer cell migration and invasion. The functional role of mitochondrial protein acetylation on cancer cell migration remains unclear. General control of amino acid synthesis 5 like-1(GCN5L1), as the regulator of mitochondrial protein acetylation, functions on metabolic reprogramming in mouse livers. In this study, we find that GCN5L1 expression is significantly decreased in metastatic HCC tissues. Loss of GCN5L1 promotes reactive oxygen species (ROS) generation through enhanced fatty acid oxidation (FAO), followed by activation of cellular ERK and DRP1 to promote mitochondrial fission and epithelia to mesenchymal transition (EMT) to boost cell migration. Moreover, palmitate and carnitine-stimulated FAO promotes mitochondrial fission and EMT gene expression to activate HCC cell migration. On the other hand, increased cellular acetyl-CoA level, the product of FAO, enhances HCC cell migration. Taken together, our finding uncovers the metastasis suppressor role as well as the underlying mechanism of GCN5L1 in HCC and also provides evidence of FAO retrograde control of HCC metastasis.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.