Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA; email:
Annu Rev Cell Dev Biol. 2020 Oct 6;36:265-289. doi: 10.1146/annurev-cellbio-021820-101354.
Maintaining mitochondrial health is essential for the survival and function of eukaryotic organisms. Misfunctioning mitochondria activate stress-responsive pathways to restore mitochondrial network homeostasis, remove damaged or toxic proteins, and eliminate damaged organelles via selective autophagy of mitochondria, a process termed mitophagy. Failure of these quality control pathways is implicated in the pathogenesis of Parkinson's disease and other neurodegenerative diseases. Impairment of mitochondrial quality control has been demonstrated to activate innate immune pathways, including inflammasome-mediated signaling and the antiviral cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING)-regulated interferon response. Immune system malfunction is a common hallmark in many neurodegenerative diseases; however, whether inflammation suppresses or exacerbates disease pathology is still unclear. The goal of this review is to provide a historical overview of the field, describe mechanisms of mitochondrial quality control, and highlight recent advances on the emerging role of mitochondria in innate immunity and inflammation.
维持线粒体健康对于真核生物的生存和功能至关重要。功能失调的线粒体激活应激反应途径，以恢复线粒体网络的动态平衡，清除受损或有毒的蛋白质，并通过线粒体的选择性自噬来消除受损的细胞器，这个过程被称为线粒体自噬。这些质量控制途径的失效与帕金森病和其他神经退行性疾病的发病机制有关。已经证明，线粒体质量控制的损害会激活先天免疫途径，包括炎性小体介导的信号转导以及抗病毒环鸟苷酸-腺苷酸合酶 (cGAS)/干扰素基因刺激因子 (STING) 调节的干扰素反应。免疫系统功能障碍是许多神经退行性疾病的共同特征；然而，炎症是抑制还是加重疾病病理学尚不清楚。本综述的目的是提供该领域的历史概述，描述线粒体质量控制的机制，并强调线粒体在先天免疫和炎症中新兴作用的最新进展。
