Department of Aging and Geriatric Research, College of Medicine, Institute on Aging, University of Florida, Gainesville, FL 32611, USA.
J Cell Sci. 2010 Aug 1;123(Pt 15):2533-42. doi: 10.1242/jcs.070490.
A decline in mitochondrial function plays a key role in the aging process and increases the incidence of age-related disorders. A deeper understanding of the intricate nature of mitochondrial dynamics, which is described as the balance between mitochondrial fusion and fission, has revealed that functional and structural alterations in mitochondrial morphology are important factors in several key pathologies associated with aging. Indeed, a recent wave of studies has demonstrated the pleiotropic role of fusion and fission proteins in numerous cellular processes, including mitochondrial metabolism, redox signaling, the maintenance of mitochondrial DNA and cell death. Additionally, mitochondrial fusion and fission, together with autophagy, have been proposed to form a quality-maintenance mechanism that facilitates the removal of damaged mitochondria from the cell, a process that is particularly important to forestall aging. Thus, dysfunctional regulation of mitochondrial dynamics might be one of the intrinsic causes of mitochondrial dysfunction, which contributes to oxidative stress and cell death during the aging process. In this Commentary, we discuss recent studies that have converged at a consensus regarding the involvement of mitochondrial dynamics in key cellular processes, and introduce a possible link between abnormal mitochondrial dynamics and aging.
线粒体功能的下降在衰老过程中起着关键作用,并增加了与年龄相关疾病的发病率。对线粒体动力学的复杂性质有了更深入的了解,线粒体动力学被描述为线粒体融合和裂变之间的平衡,这表明线粒体形态的功能和结构改变是与衰老相关的几种关键病理的重要因素。事实上,最近的一波研究表明,融合和裂变蛋白在许多细胞过程中具有多效性作用,包括线粒体代谢、氧化还原信号、线粒体 DNA 的维持和细胞死亡。此外,线粒体融合和裂变与自噬一起被提出形成一种质量维持机制,促进受损线粒体从细胞中清除,这一过程对于阻止衰老尤为重要。因此,线粒体动力学的功能失调调节可能是线粒体功能障碍的内在原因之一,线粒体功能障碍在衰老过程中会导致氧化应激和细胞死亡。在这篇评论中,我们讨论了最近的研究,这些研究在涉及线粒体动力学的关键细胞过程方面达成了共识,并介绍了异常线粒体动力学与衰老之间的可能联系。