Mitophagy in human health, ageing and disease.

Anna Picca, Julie Faitg, Johan Auwerx, Luigi Ferrucci, Davide D'Amico

Journal: Nature metabolism 2023;5(12):2047-2061

PMID: 38036770

Abstract

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.

© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

Address: Department of Medicine and Surgery, LUM University, Casamassima, Italy.; Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Rome, Italy.; Amazentis, EPFL Innovation Park, Lausanne, Switzerland.; Laboratory of Integrative Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.; Division of Intramural Research, National Institute on Aging, Baltimore, MD, USA. [email protected].; Amazentis, EPFL Innovation Park, Lausanne, Switzerland. [email protected].

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