Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.
Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA; USC Norris Comprehensive Cancer Center, Los Angeles, CA 90089, USA; Biomedical Sciences, Graduate School, Ajou University, Suwon 16499, South Korea.
Semin Cell Dev Biol. 2021 Aug;116:160-168. doi: 10.1016/j.semcdb.2021.02.006. Epub 2021 Mar 23.
Mitochondria were described as early as 1890 as ubiquitous intracellular structures by Ernster and Schatz (1981) [1]. Since then, the accretion of knowledge in the past century has revealed much of the molecular details of mitochondria, ranging from mitochondrial origin, structure, metabolism, genetics, and signaling, and their implications in health and disease. We now know that mitochondria are remarkably multifunctional and deeply intertwined with many vital cellular processes. They are quasi-self organelles that still possess remnants of its bacterial ancestry, including an independent genome. The mitochondrial free radical theory of aging (MFRTA), which postulated that aging is a product of oxidative damage to mitochondrial DNA, provided a conceptual framework that put mitochondria on the map of aging research. However, several studies have more recently challenged the general validity of the theory, favoring novel ideas based on emerging evidence to understand how mitochondria contribute to aging and age-related diseases. One prominent topic of investigation lies on the fact that mitochondria are not only production sites for bioenergetics and macromolecules, but also regulatory hubs that communicate and coordinate many vital physiological processes at the cellular and organismal level. The bi-directional communication and coordination between the co-evolved mitochondrial and nuclear genomes is especially interesting in terms of cellular regulation. Mitochondria are dynamic and adaptive, rendering their function sensitive to cellular context. Tissues with high energy demands, such as the brain, seem to be uniquely affected by age-dependent mitochondrial dysfunction, providing a foundation for the development of novel mitochondrial-based therapeutics and diagnostics.
线粒体早在 1890 年就被 Ernster 和 Schatz（1981）[1]描述为普遍存在的细胞内结构。自那时以来，一个世纪以来知识的积累揭示了线粒体的许多分子细节，包括线粒体的起源、结构、代谢、遗传和信号转导，以及它们在健康和疾病中的意义。我们现在知道，线粒体具有显著的多功能性，与许多重要的细胞过程密切交织在一起。它们是准自主细胞器，仍然保留着其细菌祖先的痕迹，包括一个独立的基因组。线粒体自由基衰老理论（MFRTA）假设衰老的产生是由于线粒体 DNA 的氧化损伤，为衰老研究提供了一个概念框架，使线粒体成为衰老研究的一个重要组成部分。然而，最近有几项研究对该理论的普遍有效性提出了挑战，倾向于基于新兴证据的新观点，以了解线粒体如何导致衰老和与衰老相关的疾病。一个突出的研究课题是，线粒体不仅是生物能量和大分子的产生场所，也是在细胞和机体水平上进行通讯和协调许多重要生理过程的调节中心。线粒体和核基因组的双向通讯和协调在细胞调节方面尤其有趣。线粒体是动态和适应性的，其功能对细胞环境敏感。高能量需求的组织，如大脑，似乎特别受到年龄相关的线粒体功能障碍的影响，为新型基于线粒体的治疗和诊断方法的发展提供了基础。
