Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland; email:
Interdisciplinary School of Health Sciences, University of Ottawa Brain and Mind Research Institute and Centre for Neuromuscular Disease, Ottawa K1H 8M5, Canada; email:
Annu Rev Pharmacol Toxicol. 2018 Jan 6;58:353-389. doi: 10.1146/annurev-pharmtox-010716-104908. Epub 2017 Sep 27.
Mitochondria are essential organelles for many aspects of cellular homeostasis, including energy harvesting through oxidative phosphorylation. Alterations of mitochondrial function not only impact on cellular metabolism but also critically influence whole-body metabolism, health, and life span. Diseases defined by mitochondrial dysfunction have expanded from rare monogenic disorders in a strict sense to now also include many common polygenic diseases, including metabolic, cardiovascular, neurodegenerative, and neuromuscular diseases. This has led to an intensive search for new therapeutic and preventive strategies aimed at invigorating mitochondrial function by exploiting key components of mitochondrial biogenesis, redox metabolism, dynamics, mitophagy, and the mitochondrial unfolded protein response. As such, new findings linking mitochondrial function to the progression or outcome of this ever-increasing list of diseases has stimulated the discovery and development of the first true mitochondrial drugs, which are now entering the clinic and are discussed in this review.
线粒体对于细胞内环境的许多方面都是必不可少的，包括通过氧化磷酸化来获取能量。线粒体功能的改变不仅会影响细胞代谢，而且还会严重影响全身代谢、健康和寿命。由线粒体功能障碍定义的疾病已经从严格意义上的罕见单基因疾病扩展到现在还包括许多常见的多基因疾病，包括代谢、心血管、神经退行性和神经肌肉疾病。这导致了对新的治疗和预防策略的深入研究，旨在通过利用线粒体生物发生、氧化还原代谢、动态、线粒体自噬和线粒体未折叠蛋白反应的关键成分来增强线粒体功能。因此，将线粒体功能与这一不断增加的疾病列表的进展或结果联系起来的新发现，刺激了第一种真正的线粒体药物的发现和开发，这些药物现在正在进入临床，并在本文中进行了讨论。
