Open Accessm-AAA and i-AAA complexes work coordinately regulating OMA1, the stress-activated supervisor of mitochondrial dynamics
Author(s) -
Francesco Consolato,
Francesca Maltecca,
Susanna Tulli,
Irene Sambri,
Giorgio Casari
Publication year - 2018
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.213546
Subject(s) - biology , microbiology and biotechnology , protease , mitochondrion , gtpase , mitochondrial matrix , inner mitochondrial membrane , aaa proteins , biochemistry , cytosol , enzyme , atpase
The proteolytic processing of dynamin like GTPase OPA1, mediated by the activity of both YME1L1 (i-AAA protease complex) and OMA1, is a crucial step in the regulation of mitochondrial dynamics. OMA1 is a zinc metallopeptidase of the inner mitochondrial membrane that undergoes pre-activating proteolytic and auto-proteolytic cleavage after mitochondrial import. Here, we identify AFG3L2 (m-AAA complex) as the major protease mediating this event by maturing the pre-pro-OMA1 of 60 kDa to the pro-OMA1 form of 40 kDa by severing the amino-terminal part without recognizing specific consensus sequence. Therefore, m-AAA and i-AAA complexes coordinately regulate OMA1 processing and turnover, and consequently OPA1 isoforms, thus adding new information in the comprehension of the molecular mechanisms in mitochondrial dynamics and of neurodegenerative diseases affected by these phenomena.