Interplay of mitochondrial fission-fusion with cell cycle regulation: Possible impacts on stem cell and organismal aging.

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.

线粒体功能和内稳态的下降是衰老的一个标志。人们认识到，线粒体的作用远比产生活性氧导致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分裂或融合事件的能力会影响衰老过程。线粒体分裂和融合事件的动态平衡是维持包括细胞周期在内的关键细胞功能所必需的。具体而言，细胞周期调节因子调节线粒体分裂（和融合）机制的分子活动，以调控细胞周期进程。在这篇综述中，我们讨论了一些文献，这些文献使我们了解线粒体分裂和融合的动态平衡的改变如何调节细胞周期的进展、退出和重新进入，以及如何调节细胞的衰老。重要的是，线粒体分裂或融合的核心调节因子正逐渐成为关键的干细胞调节因子。鉴于成体干细胞的异常会促进衰老，我们在衰老的背景下讨论了这种调节在干细胞中的意义。我们还提出了一些假设，这些假设可能为进一步理解线粒体分裂 - 融合动态在衰老生物学中的作用提供方向。