Editorial: Special Issue on mitochondrial fidelity.
Editorial: Special Issue on mitochondrial fidelity.
复制标题
社论：线粒体保真度特刊。
DOI：
10.1016/j.mito.2019.12.007
复制
发表时间：
2020
期刊：
影响因子：
4.4
通讯作者：
Khalimonchuk,Oleh
中科院分区：
文献类型：
--
作者：
Khalimonchuk,Oleh
线粒体是复杂和高度动态的细胞器，对大量重要的细胞功能至关重要。除了在生物能量学中早已为人所知的作用外，线粒体现在被认为是关键的信号和代谢中心，对细胞生理至关重要。除了三磷酸腺苷外，线粒体还能产生各种重要的辅因子，如血红素和铁硫簇，以及各种脂质、蛋白质和核酸的代谢前体。此外，线粒体在调节离子动态平衡和产生代谢副产物如活性氧等方面起着重要作用。后两种功能与细胞器间的通讯和细胞信号传递相互交织在一起。鉴于线粒体的最重要的生理意义，进行性线粒体功能障碍和线粒体蛋白、氧化还原和代谢稳态衰竭-以下称为线粒体保真度-已成为与年龄相关的疾病的中心因素，如心血管疾病、神经退行性疾病、听力和视力丧失以及认知能力下降。线粒体健康的关键挑战包括：(I)细胞器的复杂蛋白质环境，细胞合成的大量异常线粒体蛋白质不断挑战这种环境；(Ii)线粒体呼吸的副产品产生的氧自由基；以及(Iii)细胞器产生和利用的固有反应性辅因子和代谢物。线粒体及其复杂的动态平衡网络涉及多个高度保守的动态过程和途径，以适应动态平衡挑战和随时间变化。在正常和应激条件下，这些机制处于保护线粒体功能和完整性的前沿。这些机制的多方面生物学作用与线粒体的功能完整性和正常的细胞生理高度相关。因此，深入了解线粒体保真度背后的机制将进一步阐明它们在正常和疾病状态下的不同生物学作用。
Mitochondria are complex and highly dynamic organelles that are pivotal to a plethora of vital cellular functions. Besides their long-known role in bioenergetics, mitochondria are now recognized as critical signaling and metabolic hubs that are central to cellular physiology. In addition to ATP, mitochondria generate a variety of essential cofactors such as heme and iron-sulfur clusters and various metabolic precursors for lipids, proteins, and nucleic acids. Furthermore, mitochondria play an important role in regulating ion homeostasis and producing metabolic byproducts such as reactive oxygen species. The latter two functions are intertwined with inter-organellar communication and cellular signaling.Given the paramount physiological significance of mitochondria, it is not surprising that progressive mitochondrial dysfunction and failing mitochondrial protein, redox, and metabolic homeostasis–hereinafter referred to as mitochondrial fidelity–have emerged as central factors in age-related diseases such as cardiovascular disorders, neurodegeneration, hearing and vision loss, and cognitive decline. Key challenges for mitochondrial wellbeing include:(i) the organelle’s complex protein environment, which is constantly challenged by substantial amounts of aberrant mitochondrial proteins synthesized by cells;(ii) oxygen radicals generated as a byproduct of mitochondrial respiration; and (iii) inherently reactive cofactors and metabolites produced and utilized by the organelle. The mitochondria and its complex homeostasis network involve multiple highly conserved dynamic processes and pathways that adapt to homeostatic challenges and change over time. These mechanisms are at the forefront of safeguarding mitochondrial functions and integrity under normal and stress conditions. The multifaceted biological roles of these mechanisms are highly relevant to both functional integrity of mitochondria and normal cellular physiology. As such, a deeper understanding of the mechanisms behind mitochondrial fidelity will further elucidate their diverse biological roles in normal and disease states.