Molecular Biology of the Cell click for ASCB 2010 Annual Meeting page

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Originally published as MBoC in Press, 10.1091/mbc.E09-03-0218 on August 5, 2009

Vol. 20, Issue 19, 4216-4224, October 1, 2009

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Materials
Right arrow All Versions of this Article:
E09-03-0218v1
20/19/4216    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Koppen, M.
Right arrow Articles by Langer, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Koppen, M.
Right arrow Articles by Langer, T.

Autocatalytic Processing of m-AAA Protease Subunits in Mitochondria

Mirko Koppen*,{dagger}, Florian Bonn*, Sarah Ehses*, and Thomas Langer*,{ddagger}

*Institute for Genetics, Centre for Molecular Medicine (CMMC), Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50674 Cologne, Germany; and {ddagger}Max-Planck-Institute for Biology of Aging, 50931 Cologne, Germany

Submitted March 17, 2009; Revised July 21, 2009; Accepted July 23, 2009
Monitoring Editor: Janet M. Shaw

m-AAA proteases are ATP-dependent proteolytic machines in the inner membrane of mitochondria which are crucial for the maintenance of mitochondrial activities. Conserved nuclear-encoded subunits, termed paraplegin, Afg3l1, and Afg3l2, form various isoenzymes differing in their subunit composition in mammalian mitochondria. Mutations in different m-AAA protease subunits are associated with distinct neuronal disorders in human. However, the biogenesis of m-AAA protease complexes or of individual subunits is only poorly understood. Here, we have examined the processing of nuclear-encoded m-AAA protease subunits upon import into mitochondria and demonstrate autocatalytic processing of Afg3l1 and Afg3l2. The mitochondrial processing peptidase MPP generates an intermediate form of Afg3l2 that is matured autocatalytically. Afg3l1 or Afg3l2 are also required for maturation of newly imported paraplegin subunits after their cleavage by MPP. Our results establish that mammalian m-AAA proteases can act as processing enzymes in vivo and reveal overlapping activities of Afg3l1 and Afg3l2. These findings might be of relevance for the pathogenesis of neurodegenerative disorders associated with mutations in different m-AAA protease subunits.

This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E09-03-0218) on August 5, 2009.

{dagger} Present address: Department of Cell Biology, University of Geneva, 1207 Geneva, Switzerland.

Address correspondence to: Thomas Langer (Thomas.Langer{at}uni-koeln.de).




This article has been cited by other articles:


Home page
 JCBHome page
S. Ehses, I. Raschke, G. Mancuso, A. Bernacchia, S. Geimer, D. Tondera, J.-C. Martinou, B. Westermann, E. I. Rugarli, and T. Langer
Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1
J. Cell Biol., December 28, 2009; 187(7): 1023 - 1036.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Copyright © 2009 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.