Mitochondria, autophagy and age-associated neurodegenerative diseases: New insights into a complex interplay.
Mitochondria represent the major bioenergetic hub coordinating cellular and organismal homeostasis. The underlying causes of many pathologies tormenting humans converge on impaired mitochondrial maintenance. Mitochondria-specific autophagy (mitophagy), a cellular catabolic process targeting mitochondria, holds a prominent role in mitochondrial quality control. In addition to core autophagic machinery components, mitophagy exploits a variety of molecules that identify damaged or superfluous mitochondria and mediate their elimination. Signaling pathways integrating environmental and genetic stimuli interact with key mitophagy effectors to activate cellular stress response mechanisms, ultimately modulating health and lifespan. Here, we review the signaling cascades and molecular mechanisms that govern the process of mitophagy and discuss their involvement in ageing and neurodegeneration. This article is part of a Special Issue entitled: Mitochondrial Dysfunction in Aging.
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Crete, Greece.
Eirini
E
Lionaki
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Crete, Greece.
Maria
M
Markaki
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Crete, Greece; Department of Biology, University of Crete, Heraklion, Crete, Greece.
Konstantinos
K
Palikaras
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Crete, Greece; Department of Basic Sciences, Faculty of Medicine, University of Crete, Heraklion 70013, Crete, Greece. Electronic address: tavernarakis@imbb.forth.gr.
Nektarios
N
Tavernarakis
D000375:Aging; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology
Energy homeostasis; Mitophagy; Neurodegenerative diseases; PINK1; Parkin; Stress response