Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
J Hematol Oncol. 2022 Jul 21;15(1):98. doi: 10.1186/s13045-022-01317-0.
Mitochondria are essential for tumor growth and progression. However, the heavy demand for mitochondrial activity in cancer leads to increased production of mitochondrial reactive oxygen species (mtROS), accumulation of mutations in mitochondrial DNA, and development of mitochondrial dysfunction. If left unchecked, excessive mtROS can damage and unfold proteins in the mitochondria to an extent that becomes lethal to the tumor. Cellular systems have evolved to combat mtROS and alleviate mitochondrial stress through a quality control mechanism called the mitochondrial unfolded protein response (UPR). The UPR system is composed of chaperones and proteases, which promote protein folding or eliminate mitochondrial proteins damaged by mtROS, respectively. UPR is conserved and activated in cancer in response to mitochondrial stress to maintain mitochondrial integrity and support tumor growth. In this review, we discuss how mitochondria become dysfunctional in cancer and highlight the tumor-promoting functions of key components of the UPR.
线粒体对于肿瘤的生长和进展至关重要。然而，癌症中线粒体活性的高需求导致线粒体活性氧（mtROS）的产生增加，线粒体 DNA 突变的积累，以及线粒体功能障碍的发展。如果不加控制，过多的 mtROS 会损害线粒体中的蛋白质并使其展开，以至于对肿瘤具有致命性。细胞系统已经进化出一种称为线粒体未折叠蛋白反应（UPR）的质量控制机制来对抗 mtROS 并减轻线粒体应激。UPR 系统由伴侣蛋白和蛋白酶组成，它们分别促进蛋白质折叠或消除由 mtROS 损伤的线粒体蛋白。UPR 在癌症中是保守的，并被激活以响应线粒体应激来维持线粒体完整性并支持肿瘤生长。在这篇综述中，我们讨论了线粒体在癌症中如何变得功能失调，并强调了 UPR 的关键组成部分的肿瘤促进功能。
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