Department of Biology, University of Rome "Tor Vergata", 00133, Rome, Italy.
Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street, London, NW10TU, UK.
Cell Mol Life Sci. 2021 Apr;78(8):3767-3775. doi: 10.1007/s00018-021-03770-5. Epub 2021 Feb 23.
Preservation of mitochondrial quality is paramount for cellular homeostasis. The integrity of mitochondria is guarded by the balanced interplay between anabolic and catabolic mechanisms. The removal of bio-energetically flawed mitochondria is mediated by the process of mitophagy; the impairment of which leads to the accumulation of defective mitochondria which signal the activation of compensatory mechanisms to the nucleus. This process is known as the mitochondrial retrograde response (MRR) and is enacted by Reactive Oxygen Species (ROS), Calcium (Ca), ATP, as well as imbalanced lipid and proteostasis. Central to this mitochondria-to-nucleus signalling are the transcription factors (e.g. the nuclear factor kappa-light-chain-enhancer of activated B cells, NF-κB) which drive the expression of genes to adapt the cell to the compromised homeostasis. An increased degree of cellular proliferation is among the consequences of the MRR and as such, engagement of mitochondrial-nuclear communication is frequently observed in cancer. Mitophagy and the MRR are therefore interlinked processes framed to, respectively, prevent or compensate for mitochondrial defects.In this review, we discuss the available knowledge on the interdependency of these processes and their contribution to cell signalling in cancer.
维持线粒体质量对于细胞内稳态至关重要。线粒体的完整性由合成代谢和分解代谢机制之间的平衡相互作用来保护。通过自噬作用清除生物能量缺陷的线粒体; 自噬作用的损伤会导致缺陷线粒体的积累，从而激活细胞核的补偿机制。这个过程被称为线粒体逆行反应 (MRR)，由活性氧 (ROS)、钙 (Ca)、ATP 以及不平衡的脂质和蛋白质稳态来调节。线粒体到细胞核信号转导的核心是转录因子（例如核因子 kappa 轻链增强子的 B 细胞激活因子，NF-κB），它们驱动基因的表达，使细胞适应受损的内稳态。MRR 的一个后果是细胞增殖程度的增加，因此，线粒体-核通讯的参与在癌症中经常观察到。自噬作用和 MRR 是相互关联的过程，分别旨在预防或补偿线粒体缺陷。在这篇综述中，我们讨论了这些过程的相互依存性及其对癌症中细胞信号转导的贡献的现有知识。
