Department of Genetics, University of Alabama at Birmingham, Birmingham, USA.
School of Biosciences, University of Kent, Canterbury, Kent, UK.
Exp Gerontol. 2020 Jul 1;135:110919. doi: 10.1016/j.exger.2020.110919. Epub 2020 Mar 24.
Declining mitochondrial function and homeostasis is a hallmark of aging. It is appreciated that the role of mitochondria is much more complex than generating reactive oxygen species to cause aging-related tissue damage. More recent literature describes that the ability of mitochondria to undergo fission or fusion events with each other impacts aging processes. A dynamic balance of mitochondrial fission and fusion events is required to sustain critical cellular functions including cell cycle. Specifically, cell cycle regulators modulate molecular activities of the mitochondrial fission (and fusion) machinery towards regulating cell cycle progression. In this review, we discus literature leading to our understanding on how shifts in the dynamic balance of mitochondrial fission and fusion can modulate progression through, exit from, and re-entry to the cell cycle or in undergoing senescence. Importantly, core regulators of mitochondrial fission or fusion are emerging as crucial stem cell regulators. We discuss the implication of such regulation in stem cells in the context of aging, given that aberrations in adult stem cells promote aging. We also propose a few hypotheses that may provide direction for further understanding about the roles of mitochondrial fission-fusion dynamics in aging biology.
线粒体功能和动态平衡的下降是衰老的一个标志。人们已经认识到，线粒体的作用远比产生活性氧物质导致与衰老相关的组织损伤要复杂得多。最近的文献描述了线粒体之间发生裂变或融合事件的能力对衰老过程的影响。线粒体裂变和融合事件的动态平衡对于维持包括细胞周期在内的关键细胞功能是必需的。具体来说，细胞周期调节剂调节线粒体分裂（和融合）机制的分子活性，以调节细胞周期的进展。在这篇综述中，我们讨论了文献，这些文献使我们了解到线粒体裂变和融合的动态平衡的变化如何调节细胞周期的进展、退出和重新进入，或者发生衰老。重要的是，线粒体裂变或融合的核心调节剂正在成为关键的干细胞调节剂。我们讨论了这种调节在衰老背景下对干细胞的影响，因为成年干细胞的异常会促进衰老。我们还提出了一些假设，这些假设可能为进一步了解线粒体裂变-融合动力学在衰老生物学中的作用提供了方向。
