Guo Lishu, Gu Zhenglong
Center for Mitochondrial Genetics and Health, Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China.
Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Front Oncol. 2023 Jul 3;13:1207603. doi: 10.3389/fonc.2023.1207603. eCollection 2023.
F-ATP synthase inhibitory factor 1 (IF1) is an intrinsic inhibitor of F-ATP synthase. It is known that IF1 mediates metabolic phenotypes and cell fate, yet the molecular mechanisms through which IF1 fulfills its physiological functions are not fully understood. Ablation of IF1 favors metabolic switch to oxidative metabolism from glycolysis. c-Myc and PGC1α are critical for metabolic reprogramming. This work identified that IF1 interacted with Thr-58 phosphorylated c-Myc, which might thus mediate the activity of c-Myc and promote glycolysis. The interaction of IF1 with PGC1α inhibited oxidative respiration. c-Myc and PGC1α were localized to mitochondria under mitochondrial stress in an IF1-dependent manner. Furthermore, IF1 was found to be required for the protective effect of hypoxia on c-Myc- and PGC1α-induced cell death. This study suggested that the interactions of IF1 with transcription factors c-Myc and PGC1α might be involved in IF1-regulatory metabolic reprogramming and cell fate.
F-ATP合酶抑制因子1（IF1）是F-ATP合酶的一种内在抑制剂。已知IF1介导代谢表型和细胞命运，但其实现生理功能的分子机制尚未完全阐明。IF1的缺失有利于代谢从糖酵解向氧化代谢转变。c-Myc和PGC1α对代谢重编程至关重要。这项研究发现IF1与苏氨酸58磷酸化的c-Myc相互作用，这可能因此介导c-Myc的活性并促进糖酵解。IF1与PGC1α的相互作用抑制氧化呼吸。在IF1依赖的方式下，线粒体应激时c-Myc和PGC1α定位于线粒体。此外，发现IF1是缺氧对c-Myc和PGC1α诱导的细胞死亡产生保护作用所必需的。这项研究表明，IF1与转录因子c-Myc和PGC1α的相互作用可能参与IF1调节的代谢重编程和细胞命运。
