Mitophagy in human health, ageing and disease.
Anna PiccaJulie FaitgJohan AuwerxLuigi FerruciDavide D'AmicoPublished in: Nature metabolism (2023)
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.
Keyphrases
- human health
- nlrp inflammasome
- oxidative stress
- risk assessment
- healthcare
- physical activity
- public health
- gene expression
- endothelial cells
- dna damage
- signaling pathway
- high intensity
- cell death
- brain injury
- blood brain barrier
- bone marrow
- reactive oxygen species
- deep learning
- gram negative
- endoplasmic reticulum stress