Cell signaling and mitochondrial dynamics: Implications for neuronal function and neurodegenerative disease

Theodore J Wilson; Andrew M Slupe; Stefan Strack

doi:10.1016/j.nbd.2012.01.009

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Cell signaling and mitochondrial dynamics: Implications for neuronal function and neurodegenerative disease

Journal article

Open access

Peer reviewed

Cell signaling and mitochondrial dynamics: Implications for neuronal function and neurodegenerative disease

Theodore J Wilson, Andrew M Slupe and Stefan Strack

Neurobiology of disease, Vol.51, pp.13-26

03/2013

DOI: 10.1016/j.nbd.2012.01.009

PMCID: PMC3383441

PMID: 22297163

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https://doaj.org/article/8b8e1247d85a4fe3ade895d11220a60dView

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Abstract

Nascent evidence indicates that mitochondrial fission, fusion, and transport are subject to intricate regulatory mechanisms that intersect with both well-characterized and emerging signaling pathways. While it is well established that mutations in components of the mitochondrial fission/fusion machinery can cause neurological disorders, relatively little is known about upstream regulators of mitochondrial dynamics and their role in neurodegeneration. Here, we review posttranslational regulation of mitochondrial fission/fusion enzymes, with particular emphasis on dynamin-related protein 1 (Drp1), as well as outer mitochondrial signaling complexes involving protein kinases and phosphatases. We also review recent evidence that mitochondrial dynamics has profound consequences for neuronal development and synaptic transmission and discuss implications for clinical translation. ► Mitochondrial fission/fusion enzymes are regulated by diverse posttranslational modifications. ► Phosphorylation of the fission enzyme Drp1 regulates neuronal survival and development. ► Outer-mitochondrial kinase/phosphatase signaling complexes control mitochondrial shape. ► Spinocerebellar ataxia 12 may involve dysregulated phosphatase signaling at mitochondria. ► Mitochondrial dynamics impacts bioenergetics and Ca2+ signaling in neurons.

Mitochondrial fusion

Charcot–Marie–Tooth disease

Mitofusin

Optic atrophy 1

Synaptogenesis

Neurodegeneration

Synaptic transmission

Dynamin-related protein 1

Mitochondrial transport

Autosomal dominant optic atrophy

Protein phosphorylation

Mitochondrial fission

Details

Title: Subtitle: Cell signaling and mitochondrial dynamics: Implications for neuronal function and neurodegenerative disease
Creators: Theodore J Wilson - Department of Molecular and Cellular Biology Program, University of Iowa, Carver College of Medicine, Iowa City, IA, USA
Andrew M Slupe - Department of Pharmacology, University of Iowa, Carver College of Medicine, Iowa City, IA, USA
Stefan Strack - Department of Pharmacology, University of Iowa, Carver College of Medicine, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Neurobiology of disease, Vol.51, pp.13-26
DOI: 10.1016/j.nbd.2012.01.009
PMID: 22297163
PMCID: PMC3383441
NLM abbreviation: Neurobiol Dis
ISSN: 0969-9961
eISSN: 1095-953X
Publisher: Elsevier Inc
Language: English
Date published: 03/2013
Academic Unit: Pathology; Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984040447102771

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