Tongji University Cancer Center, Shanghai Tenth People's Hospital of Tongji University, School of Medicine, Tongji University, Shanghai 200092, China.
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Int J Biol Sci. 2023 Jan 16;19(3):897-915. doi: 10.7150/ijbs.81609. eCollection 2023.
Mitochondria are intracellular organelles involved in energy production, cell metabolism and cell signaling. They are essential not only in the process of ATP synthesis, lipid metabolism and nucleic acid metabolism, but also in tumor development and metastasis. Mutations in mtDNA are commonly found in cancer cells to promote the rewiring of bioenergetics and biosynthesis, various metabolites especially oncometabolites in mitochondria regulate tumor metabolism and progression. And mutation of enzymes in the TCA cycle leads to the unusual accumulation of certain metabolites and oncometabolites. Mitochondria have been demonstrated as the target for cancer treatment. Cancer cells rely on two main energy resources: oxidative phosphorylation (OXPHOS) and glycolysis. By manipulating OXPHOS genes or adjusting the metabolites production in mitochondria, tumor growth can be restrained. For example, enhanced complex I activity increases NAD/NADH to prevent metastasis and progression of cancers. In this review, we discussed mitochondrial function in cancer cell metabolism and specially explored the unique role of mitochondria in cancer stem cells and the tumor microenvironment. Targeting the OXPHOS pathway and mitochondria-related metabolism emerging as a potential therapeutic strategy for various cancers.
线粒体是参与能量产生、细胞代谢和细胞信号转导的细胞内细胞器。它们不仅在 ATP 合成、脂质代谢和核酸代谢过程中必不可少，而且在肿瘤发生和转移中也起着关键作用。线粒体 DNA 的突变在癌细胞中很常见，促进生物能量学和生物合成的重新布线，线粒体中的各种代谢物特别是致癌代谢物调节肿瘤代谢和进展。三羧酸循环中酶的突变导致某些代谢物和致癌代谢物的异常积累。线粒体已被证明是癌症治疗的靶点。癌细胞依赖两种主要的能量来源：氧化磷酸化（OXPHOS）和糖酵解。通过操纵 OXPHOS 基因或调节线粒体中代谢物的产生，可以抑制肿瘤生长。例如，增强复合物 I 活性增加 NAD/NADH 以防止癌症的转移和进展。在这篇综述中，我们讨论了线粒体在癌细胞代谢中的功能，并特别探讨了线粒体在癌症干细胞和肿瘤微环境中的独特作用。靶向 OXPHOS 途径和与线粒体相关的代谢已成为各种癌症的潜在治疗策略。
