Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
Biochim Biophys Acta Mol Cell Res. 2019 Apr;1866(4):575-587. doi: 10.1016/j.bbamcr.2018.12.012. Epub 2018 Dec 28.
Mitochondria are the energy producing dynamic double-membraned organelles essential for cellular and organismal survival. A multitude of intra- and extra-cellular signals involved in the regulation of energy metabolism and cell fate determination converge on mitochondria to promote or prevent cell survival by modulating mitochondrial function and structure. Mitochondrial fitness is maintained by mitophagy, a pathway of selective degradation of dysfunctional organelles. Mitophagy impairment and altered clearance results in increased levels of dysfunctional and structurally aberrant mitochondria, changes in energy production, loss of responsiveness to intra- and extra-cellular signals and ultimately cell death. The decline of mitochondrial function and homeostasis with age is reported to be central to age-related pathologies. Here we discuss the molecular mechanisms controlling mitochondrial dynamics, mitophagy and cell death signalling and how their perturbation may contribute to ageing and age-related illness.
线粒体是产生能量的动态双层膜细胞器，对细胞和生物个体的生存至关重要。许多涉及能量代谢调节和细胞命运决定的细胞内和细胞外信号都汇集到线粒体，通过调节线粒体的功能和结构来促进或阻止细胞存活。线粒体通过自噬来维持其健康，这是一种选择性降解功能失调细胞器的途径。自噬功能障碍和清除异常导致功能失调和结构异常的线粒体水平增加，能量产生变化，对细胞内外信号的反应性丧失，最终导致细胞死亡。据报道，线粒体功能和动态平衡随年龄的下降是与年龄相关的病理学的核心。在这里，我们讨论了控制线粒体动力学、自噬和细胞死亡信号的分子机制，以及它们的失调如何导致衰老和与年龄相关的疾病。
