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Disturbed mitochondrial dynamics and neurodegenerative disorders

Lookup NU author(s): Dr Florence Burte, Professor Patrick Chinnery, Dr Patrick Yu Wai Man

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Abstract

Mitochondria form a highly interconnected tubular network throughout the cell via a dynamic process, with mitochondrial segments fusing and breaking apart continuously. Strong evidence has emerged to implicate disturbed mitochondrial fusion and fission as central pathological components underpinning a number of childhood and adult-onset neurodegenerative disorders. Several proteins that regulate the morphology of the mitochondrial network have been identified, the most widely studied of which are optic atrophy 1 and mitofusin 2. Pathogenic mutations that disrupt these two pro-fusion proteins cause autosomal dominant optic atrophy and axonal Charcot-Marie-Tooth disease type 2A, respectively. These disorders predominantly affect specialized neurons that require precise shuttling of mitochondria over long axonal distances. Considerable insight has also been gained by carefully dissecting the deleterious consequences of imbalances in mitochondrial fusion and fission on respiratory chain function, mitochondrial quality control (mitophagy), and programmed cell death. Interestingly, these cellular processes are also implicated in more-common complex neurodegenerative disorders, such as Alzheimer disease and Parkinson disease, indicating a common pathological thread and a close relationship with mitochondrial structure, function and localization. Understanding how these fundamental processes become disrupted will prove crucial to the development of therapies for the growing number of neurodegenerative disorders linked to disturbed mitochondrial dynamics.


Publication metadata

Author(s): Chinnery PF; Yu-Wai-Man P; Burte F; Carelli V

Publication type: Review

Publication status: Published

Journal: Nature Reviews Neurology

Year: 2015

Volume: 11

Issue: 1

Pages: 11-24

Print publication date: 01/01/2015

Online publication date: 09/12/2014

ISSN (print): 1759-4758

ISSN (electronic): 1759-4766

Publisher: NATURE PUBLISHING GROUP

URL: http://dx.doi.org/10.1038/nrneurol.2014.228

DOI: 10.1038/nrneurol.2014.228


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