English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1

Ehses, S., Raschke, I., Mancuso, G., Bernacchia, A., Geimer, S., Tondera, D., et al. (2009). Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1. J Cell Biol, 187(7), 1023-36. doi:10.1083/jcb.200906084.

Item is

Files

show Files

Locators

show
hide
Description:
-
OA-Status:
Not specified

Creators

show
hide
 Creators:
Ehses, S., Author
Raschke, I., Author
Mancuso, G., Author
Bernacchia, A., Author
Geimer, S., Author
Tondera, D., Author
Martinou, J. C., Author
Westermann, B., Author
Rugarli, E. I., Author
Langer, T.1, Author           
Affiliations:
1Department Langer - Mitochondrial Proteostasis, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_3393994              

Content

show
hide
Free keywords: ATP-Dependent Proteases ATPases Associated with Diverse Cellular Activities Adenosine Triphosphatases/metabolism Animals Cells, Cultured Enzyme Stability GTP Phosphohydrolases/genetics/*metabolism Humans Isoenzymes/genetics/metabolism/physiology Metalloendopeptidases/genetics/metabolism/*physiology Metalloproteases/genetics/metabolism/*physiology Mice Mitochondria/*metabolism Mitochondrial Proteins/genetics/metabolism/*physiology RNA Interference
 Abstract: Mitochondrial fusion depends on the dynamin-like guanosine triphosphatase OPA1, whose activity is controlled by proteolytic cleavage. Dysfunction of mitochondria induces OPA1 processing and results in mitochondrial fragmentation, allowing the selective removal of damaged mitochondria. In this study, we demonstrate that two classes of metallopeptidases regulate OPA1 cleavage in the mitochondrial inner membrane: isoenzymes of the adenosine triphosphate (ATP)-dependent matrix AAA (ATPase associated with diverse cellular activities [m-AAA]) protease, variable assemblies of the conserved subunits paraplegin, AFG3L1 and -2, and the ATP-independent peptidase OMA1. Functionally redundant isoenzymes of the m-AAA protease ensure the balanced accumulation of long and short isoforms of OPA1 required for mitochondrial fusion. The loss of AFG3L2 in mouse tissues, down-regulation of AFG3L1 and -2 in mouse embryonic fibroblasts, or the expression of a dominant-negative AFG3L2 variant in human cells decreases the stability of long OPA1 isoforms and induces OPA1 processing by OMA1. Moreover, cleavage by OMA1 causes the accumulation of short OPA1 variants if mitochondrial DNA is depleted or mitochondrial activities are impaired. Our findings link distinct peptidases to constitutive and induced OPA1 processing and shed new light on the pathogenesis of neurodegenerative disorders associated with mutations in m-AAA protease subunits.

Details

show
hide
Language(s):
 Dates: 2009-12-282009-12-30
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: Other: 20038678
DOI: 10.1083/jcb.200906084
ISSN: 1540-8140 (Electronic)0021-9525 (Linking)
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: J Cell Biol
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 187 (7) Sequence Number: - Start / End Page: 1023 - 36 Identifier: -