Autocatalytic Processing of m-AAA Protease Subunits in Mitochondria

被引:38
作者
Koppen, Mirko [1 ]
Bonn, Florian [1 ]
Ehses, Sarah [1 ]
Langer, Thomas [1 ,2 ]
机构
[1] Univ Cologne, Inst Genet, Ctr Mol Med CMMC, Cologne Excellence Cluster Cellular Stress Respon, D-50674 Cologne, Germany
[2] Max Planck Inst Biol Aging, D-50931 Cologne, Germany
基金
欧洲研究理事会;
关键词
HEREDITARY SPASTIC PARAPLEGIA; PROTEOLYTIC CLEAVAGE; OPA1; METALLOPROTEASE; TRANSLOCATION; DEGENERATION; DEGRADATION; IMPAIRMENT; MORPHOLOGY; APOPTOSIS;
D O I
10.1091/mbc.E09-03-0218
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:4216 / 4224
页数:9
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