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Neuronal Mitophagy: Lessons from a Pathway Linked to Parkinson’s Disease

  • Olga CortiEmail author
Original Article

Abstract

Neurons are specialized cells with complex and extended architecture and high energy requirements. Energy in the form of adenosine triphosphate, produced essentially by mitochondrial respiration, is necessary to preserve neuronal morphology, maintain resting potential, fire action potentials, and ensure neurotransmission. Pools of functional mitochondria are required in all neuronal compartments, including cell body and dendrites, nodes of Ranvier, growth cones, axons, and synapses. The mechanisms by which old or damaged mitochondria are removed and replaced in neurons remain to be fully understood. Mitophagy has gained considerable interest since the discovery of familial forms of Parkinson’s disease caused by dysfunction of PINK1 and Parkin, two multifunctional proteins cooperating in the regulation of this process. Over the past 10 years, the molecular mechanisms by which PINK1 and Parkin jointly promote the degradation of defective mitochondria by autophagy have been dissected. However, our understanding of the relevance of mitophagy to mitochondrial homeostasis in neurons remains poor. Insight has been recently gained thanks to the development of fluorescent reporter systems for tracking mitochondria in the acidic compartment of the lysosome. Using these tools, mitophagy events have been visualized in primary neurons in culture and in vivo, under basal conditions and in response to toxic insults. Despite these advances, whether PINK1 and Parkin play a major role in promoting neuronal mitophagy under physiological conditions in adult animals and during aging remains a matter of debate. Future studies will have to clarify in how far dysfunction of neuronal mitophagy is central to the pathophysiology of Parkinson’s disease.

Keywords

Mitophagy Parkinson’s disease PINK1 and Parkin-dependent mitochondrial quality control Aging Mitochondrial stress Fluorescent mitophagy reporters 

Notes

Funding Information

Our work is supported by the Institut national de la santé et de la recherche médicale (INSERM), Fondation Institut du Cerveau et de la Moelle épinière and Agence Nationale pour la Recherche (“Investissements d’avenir,” grant ANR-10-IAIHU-06), Fondation de France, Association France Parkinson, and Michael J. Fox Foundation.

Compliance with Ethical Standards

Conflict of Interest

The author declares that she has no conflict of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institut du Cerveau et de la Moelle épinière, ICMParisFrance
  2. 2.Inserm, U1127ParisFrance
  3. 3.CNRS, UMR 7225ParisFrance
  4. 4.Sorbonne UniversitésParisFrance

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