da Veiga Moreira Jorgelindo, Schwartz Laurent, Jolicoeur Mario
Research Laboratory in Applied Metabolic Engineering, Department of Chemical Engineering, Polytechnique Montréal, Montréal, QC, Canada.
Assistance Publique des Hôpitaux de Paris, Paris, France.
Front Oncol. 2020 Sep 18;10:573399. doi: 10.3389/fonc.2020.573399. eCollection 2020.
The occurrence of mitochondrial respiration has allowed evolution toward more complex and advanced life forms. However, its dysfunction is now also seen as the most probable cause of one of the biggest scourges in human health, cancer. Conventional cancer treatments such as chemotherapy, which mainly focus on disrupting the cell division process, have shown being effective in the attenuation of various cancers but also showing significant limits as well as serious sides effects. Indeed, the idea that cancer is a metabolic disease with mitochondria as the central site of the pathology is now emerging, and we provide here a review supporting this "novel" hypothesis re-actualizing past century Otto Warburg's thoughts. Our conclusion, while integrating literature, is that mitochondrial activity and, in particular, the activity of cytochrome c oxidase, complex IV of the ETC, plays a fundamental role in the effectiveness or non-effectiveness of chemotherapy, immunotherapy and probably radiotherapy treatments. We therefore propose that cancer cells mitochondrial singlet oxygen (O) dynamics may be an efficient target for metabolic therapy development.
线粒体呼吸作用的出现使得生物能够向更复杂、更高级的生命形式进化。然而，现在人们也认为线粒体功能障碍是人类健康领域最大的灾难之一——癌症——最可能的病因。传统的癌症治疗方法，如化疗，主要侧重于干扰细胞分裂过程，已证明对减轻各种癌症有效，但也存在显著局限性和严重的副作用。事实上，认为癌症是一种以线粒体为病理中心部位的代谢性疾病的观点正在兴起，我们在此提供一篇综述来支持这一“新颖”的假说，该假说重新唤起了上个世纪奥托·瓦尔堡的思想。我们的结论在整合文献的基础上认为，线粒体活性，特别是细胞色素c氧化酶（电子传递链复合体IV）的活性，在化疗、免疫疗法以及可能的放射治疗的有效性或无效性方面起着根本性作用。因此，我们提出癌细胞线粒体单线态氧（O）动力学可能是代谢疗法开发的一个有效靶点。
