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线粒体自噬:与癌症发展和治疗的关联

Mitophagy: Link to cancer development and therapy.

作者信息

Kulikov Andrey V, Luchkina Ekaterina A, Gogvadze Vladimir, Zhivotovsky Boris

机构信息

Faculty of Basic Medicine, MV Lomonosov Moscow State University, 119991 Moscow, Russia.

Faculty of Basic Medicine, MV Lomonosov Moscow State University, 119991 Moscow, Russia; Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177 Stockholm, Sweden.

出版信息

Biochem Biophys Res Commun. 2017 Jan 15;482(3):432-439. doi: 10.1016/j.bbrc.2016.10.088. Epub 2017 Feb 3.

Abstract

Mitophagy, the selective degradation of mitochondria via the autophagic pathway, is a vital mechanism of mitochondrial quality control in cells. Mitophagy is responsible for the removal of malfunctioning or damaged mitochondria, which is essential for normal cellular physiology and tissue development. Pathways involved in the regulation of mitophagy, tumorigenesis, and cell death are overlapping in many cases and may be triggered by common upstream signals, which converge at the mitochondria. The failure to properly modulate mitochondrial turnover in response to oncogenic stresses can either stimulate or suppress tumorigenesis. Thus, the analysis of crosstalk among the processes of mitophagy, cell death and tumorigenesis is important for the identification of targets responsible for the stimulation of cell death and selective elimination of cancer cells. In the present review, we analyze the mechanisms of mitophagy regulation, the pathways underlying the utilization of damaged mitochondria, and how intervention with mitophagy can affect tumor cell resistance to treatment.

摘要

线粒体自噬是通过自噬途径对线粒体进行选择性降解,是细胞中线粒体质量控制的重要机制。线粒体自噬负责清除功能失调或受损的线粒体,这对正常细胞生理和组织发育至关重要。在许多情况下,参与线粒体自噬、肿瘤发生和细胞死亡调控的途径相互重叠,可能由汇聚于线粒体的共同上游信号触发。未能适当调节对致癌应激的线粒体更新可刺激或抑制肿瘤发生。因此,分析线粒体自噬、细胞死亡和肿瘤发生过程之间的相互作用对于确定负责刺激细胞死亡和选择性清除癌细胞的靶点很重要。在本综述中,我们分析了线粒体自噬调控机制、受损线粒体利用的潜在途径,以及线粒体自噬干预如何影响肿瘤细胞对治疗的抗性。

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