Boese Austin C, Kang Sumin
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Redox Biol. 2021 Jun;42:101870. doi: 10.1016/j.redox.2021.101870. Epub 2021 Jan 21.
Cancer cells display abnormal metabolic activity as a result of activated oncogenes and loss of tumor suppressor genes. The Warburg Effect is a common metabolic feature of cancer that involves a preference for aerobic glycolysis over oxidative phosphorylation to generate ATP and building blocks for biosynthesis. However, emerging evidence indicates that mitochondrial metabolic pathways are also reprogrammed in cancer and play vital roles in bioenergetics, biosynthesis, and managing redox homeostasis. The mitochondria act a central hub for metabolic pathways that generate ATP and building blocks for lipid, nucleic acid and protein biosynthesis. However, mitochondrial respiration is also a leading source of reactive oxygen species that can damage cellular organelles and trigger cell death if levels become too high. In general, cancer cells are reported to have higher levels of reactive oxygen species than their non-cancerous cells of origin, and therefore must employ diverse metabolic strategies to prevent oxidative stress. However, mounting evidence indicates that the metabolic profiles between proliferative and disseminated cancer cells are not the same. In this review, we will examine mitochondrial metabolic pathways, such as glutaminolysis, that proliferative and disseminated cancer cells utilize to control their redox status.
由于癌基因激活和肿瘤抑制基因缺失，癌细胞表现出异常的代谢活性。瓦伯格效应是癌症常见的代谢特征，即相较于氧化磷酸化，癌细胞更倾向于通过有氧糖酵解来生成ATP以及用于生物合成的原料。然而，新出现的证据表明，线粒体代谢途径在癌症中也会重新编程，并在生物能量学、生物合成以及维持氧化还原稳态中发挥重要作用。线粒体是代谢途径的核心枢纽，这些代谢途径可生成ATP以及用于脂质、核酸和蛋白质生物合成的原料。然而，线粒体呼吸也是活性氧的主要来源，如果活性氧水平过高，可能会损害细胞器并引发细胞死亡。一般而言，据报道癌细胞中的活性氧水平高于其起源的非癌细胞，因此癌细胞必须采用多种代谢策略来防止氧化应激。然而，越来越多的证据表明，增殖性癌细胞和播散性癌细胞的代谢谱并不相同。在本综述中，我们将研究增殖性癌细胞和播散性癌细胞用于控制其氧化还原状态的线粒体代谢途径，如谷氨酰胺分解。
