Autocatalytic Processing of m-AAA Protease Subunits in Mitochondria
- 1 October 2009
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 20 (19), 4216-4224
- https://doi.org/10.1091/mbc.e09-03-0218
Abstract
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.Keywords
This publication has 29 references indexed in Scilit:
- The Mitochondrial Protease AFG3L2 Is Essential for Axonal DevelopmentJournal of Neuroscience, 2008
- Quality control of mitochondria: protection against neurodegeneration and ageingThe EMBO Journal, 2008
- OPA1 Processing Reconstituted in Yeast Depends on the Subunit Composition of them-AAA Protease in MitochondriaMolecular Biology of the Cell, 2007
- Regulation of the mitochondrial dynamin-like protein Opa1 by proteolytic cleavageThe Journal of cell biology, 2007
- OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1LThe Journal of cell biology, 2007
- Protein Degradation within Mitochondria: Versatile Activities of AAA Proteases and Other PeptidasesCritical Reviews in Biochemistry and Molecular Biology, 2007
- Variable and Tissue-Specific Subunit Composition of Mitochondrial m-AAA Protease Complexes Linked to Hereditary Spastic ParaplegiaMolecular and Cellular Biology, 2007
- Regulation of mitochondrial morphology through proteolytic cleavage of OPA1The EMBO Journal, 2006
- Molecular and Functional Analyses of the Human and Mouse Genes Encoding AFG3L1, a Mitochondrial Metalloprotease Homologous to the Human Spastic Paraplegia ProteinGenomics, 2001
- The mitochondrial processing peptidase: Function and specificityCellular and Molecular Life Sciences, 1996