Department of Medicine and Surgery, LUM University, Casamassima, Italy.
Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Rome, Italy.
Nat Metab. 2023 Dec;5(12):2047-2061. doi: 10.1038/s42255-023-00930-8. Epub 2023 Nov 30.
Maintaining optimal mitochondrial function is a feature of health. Mitophagy removes and recycles damaged mitochondria and regulates the biogenesis of new, fully functional ones preserving healthy mitochondrial functions and activities. Preclinical and clinical studies have shown that impaired mitophagy negatively affects cellular health and contributes to age-related chronic diseases. Strategies to boost mitophagy have been successfully tested in model organisms, and, recently, some have been translated into clinics. In this Review, we describe the basic mechanisms of mitophagy and how mitophagy can be assessed in human blood, the immune system and tissues, including muscle, brain and liver. We outline mitophagy's role in specific diseases and describe mitophagy-activating approaches successfully tested in humans, including exercise and nutritional and pharmacological interventions. We describe how mitophagy is connected to other features of ageing through general mechanisms such as inflammation and oxidative stress and forecast how strengthening research on mitophagy and mitophagy interventions may strongly support human health.
维持最佳的线粒体功能是健康的特征。自噬作用清除和回收受损的线粒体,并调节新的、功能齐全的线粒体的生物发生,从而保持健康的线粒体功能和活性。临床前和临床研究表明,自噬作用受损会对细胞健康产生负面影响,并导致与年龄相关的慢性疾病。在模式生物中已经成功测试了增强自噬作用的策略,最近,一些策略已经转化为临床应用。在这篇综述中,我们描述了自噬作用的基本机制,以及如何在人类血液、免疫系统和组织(包括肌肉、大脑和肝脏)中评估自噬作用。我们概述了自噬作用在特定疾病中的作用,并描述了在人类中成功测试的自噬作用激活方法,包括运动和营养及药物干预。我们描述了自噬作用如何通过炎症和氧化应激等一般机制与衰老的其他特征联系起来,并预测了加强自噬作用和自噬作用干预的研究如何有力地支持人类健康。