文章：

ATP酶抑制因子1（IF1）促进瓦伯格效应，并受其S39位点磷酸化调控，该磷酸化由类蛋白激酶A活性介导。

The ATPase Inhibitory Factor 1 (IF1) Contributes to the Warburg Effect and Is Regulated by Its Phosphorylation in S39 by a Protein Kinase A-like Activity

原文发布日期：29 February 2024

DOI: 10.3390/cancers16051014

类型: Article

开放获取: 是

英文摘要：

The relevant role played by the ATPase Inhibitory Factor 1 (IF1) as a physiological in vivo inhibitor of mitochondrial ATP synthase in cancer and non-cancer cells, and in the mitochondria of different mouse tissues, as assessed in different genetic loss- and gain-of-function models of IF1 has been extensively documented. In this review we summarize our findings and those of others that favor the implication of IF1 in metabolic reprogramming to an enhanced glycolytic phenotype, which is mediated by its binding and inhibition of the ATP synthase. Moreover, we emphasize that IF1 is phosphorylated in vivo in its S39 by the c-AMP-dependent PKA activity of mitochondria to render an inactive inhibitor that is unable to interact with the enzyme, thus triggering the activation of ATP synthase. Overall, we discuss and challenge the results that argue against the role of IF1 as in vivo inhibitor of mitochondrial ATP synthase and stress that IF1 cannot be regarded solely as a pro-oncogenic protein because in some prevalent carcinomas, it prevents metastatic disease.

摘要翻译： 

ATP酶抑制因子1（IF1）作为线粒体ATP合酶的生理性体内抑制剂，在癌症与非癌细胞以及不同小鼠组织线粒体中的作用，已通过多种IF1功能缺失与功能获得遗传模型得到充分验证。本综述系统整合了我们及其他研究团队的研究成果，证实IF1通过结合并抑制ATP合酶，驱动代谢重编程向糖酵解表型增强的方向发展。特别需要指出的是，IF1在体内线粒体c-AMP依赖性PKA活性作用下发生S39位点磷酸化，转化为失活状态而无法与酶结合，从而触发ATP合酶活化。本文全面探讨并质疑了否定IF1作为线粒体ATP合酶体内抑制剂作用的研究结论，同时强调IF1不应被简单视为促癌蛋白——在某些高发癌症类型中，它实际上具有抑制转移性疾病的重要功能。

原文链接：

The ATPase Inhibitory Factor 1 (IF1) Contributes to the Warburg Effect and Is Regulated by Its Phosphorylation in S39 by a Protein Kinase A-like Activity