PuSH - Publication Server of Helmholtz Zentrum München: Proteolytic processing of OPA1 links mitochondrial dysfunction to alterations in mitochondrial morphology.

Information

Clues to quality of journals

Open Access Policy of Helmholtz Association 2016

CC Licencences

Publication Metrics

Navigation

Home

Deutsch

EVA: Electronic Publishing

New EVA Application

Research

Advanced Search

Browse by ...

... HMGU-Authors/Consortia

... Organizational Structure

... Journal

... Publication Type

... Research Data

... Arbeitsgruppen

... Publication Year

Publication overview

Statistics

Statistics (last 5 years)

OA Publications

Publish

Submit Publication

Import publication from...

...EVA

Report missing publication

Highlights

Support & Contact

Contact persons

Help

Data protection

Helmholtz Open Science

JANE Journal Estimator

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Duvezin-Caubet, S.* ; Jagasia, R. ; Wagener, J.* ; Hofmann, S.* ; Trifunovic, A.* ; Hansson, A.* ; Chomyn, A.* ; Bauer, M.F.* ; Attardi, G.* ; Larsson, N.G.* ; Neupert, W.* ; Reichert, A.S.*

Proteolytic processing of OPA1 links mitochondrial dysfunction to alterations in mitochondrial morphology.

J. Biol. Chem. 281, 37972 (2006)

Publ. Version/Full Text

DOI

	Open Access Gold

Abstract
Metrics
Extra information

Many muscular and neurological disorders are associated with mitochondrial dysfunction and are often accompanied by changes in mitochondrial morphology. Mutations in the gene encoding OPA1, a protein required for fusion of mitochondria, are associated with hereditary autosomal dominant optic atrophy type I. Here we show that mitochondrial fragmentation correlates with processing of large isoforms of OPA1 in cybrid cells from a patient with myoclonus epilepsy and ragged-red fibers syndrome and in mouse embryonic fibroblasts harboring an error-prone mitochondrial mtDNA polymerase gamma. Furthermore, processed OPA1 was observed in heart tissue derived from heart-specific TFAM knock-out mice suffering from mitochondrial cardiomyopathy and in skeletal muscles from patients suffering from mitochondrial myopathies such as myopathy encephalopathy lactic acidosis and stroke-like episodes. Dissipation of the mitochondrial membrane potential leads to fast induction of proteolytic processing of OPA1 and concomitant fragmentation of mitochondria. Recovery of mitochondrial fusion depended on protein synthesis and was accompanied by resynthesis of large isoforms of OPA1. Fragmentation of mitochondria was prevented by overexpressing OPA1. Taken together, our data indicate that proteolytic processing of OPA1 has a key role in inducing fragmentation of energetically compromised mitochondria. We present the hypothesis that this pathway regulates mitochondrial morphology and serves as an early response to prevent fusion of dysfunctional mitochondria with the functional mitochondrial network.

Impact Factor

Scopus SNIP

Web of Science
Times Cited

Scopus
Cited By

Altmetric

5.854

1.219

246

335