Abstract
Ageing in diverse species ranging from the simple nematode Caenorhabditis elegans to humans is associated with a marked decrease of neuronal function and increased susceptibility to neurodegeneration. Accumulating findings also indicate that alterations in neuronal functionality with age are associated with a decline in mitochondrial integrity and function. The rate at which a mitochondrial population is refreshed is determined by the coordination of mitochondrial biogenesis with mitophagy, a selective type of autophagy targeting damaged or superfluous mitochondria for degradation. Coupling of these opposing processes is crucial for maintaining cellular energy homeostasis, which eventually contributes to health span. Here, we focus on the role of mitophagy in nervous system function in the context of normal physiology and disease. First, we consider the progress that has been made over the last decade in elucidating the mechanisms that govern and regulate mitophagy, placing emphasis on the PINK1/Parkin-mediated mitophagy. We further discuss the contribution of mitophagy to the maintenance of neuronal homeostasis and health as well as recent findings implicating impaired mitophagy in age-related decline of the nervous system function and consequently in the pathogenesis of neurodegenerative diseases.
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We apologize to those colleagues whose work could not be referenced due to space limitations.
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D. T. is supported by HealthAge (a joint training and research program on Lifespan Regulation Mechanisms in Health and Disease – GA-812830). Work in the authors’ laboratory is funded by grants from the European Research Council (ERC-GA695190-MANNA) and the General Secretariat for Research and Innovation of the Greek Ministry of Development and Investments.
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Markaki, M., Tsagkari, D. & Tavernarakis, N. Mitophagy mechanisms in neuronal physiology and pathology during ageing. Biophys Rev 13, 955–965 (2021). https://doi.org/10.1007/s12551-021-00894-7
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DOI: https://doi.org/10.1007/s12551-021-00894-7