m-AAA and i-AAA complexes coordinate to regulate OMA1, the stress-activated supervisor of mitochondrial dynamics.
J Cell Sci
; 131(7)2018 04 09.
Article
en En
| MEDLINE
| ID: mdl-29545505
ABSTRACT
The proteolytic processing of dynamin-like GTPase OPA1, mediated by the activity of both YME1L1 [intermembrane (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 [matrix (m)-AAA complex] as the major protease mediating this event, which acts by maturing the 60â
kDa pre-pro-OMA1 to the 40â
kDa pro-OMA1 form by severing the N-terminal portion without recognizing a specific consensus sequence. Therefore, m-AAA and i-AAA complexes coordinately regulate OMA1 processing and turnover, and consequently control which OPA1 isoforms are present, thus adding new information on the molecular mechanisms of mitochondrial dynamics and neurodegenerative diseases affected by these phenomena.This article has an associated First Person interview with the first author of the paper.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Metaloendopeptidasas
/
Proteasas ATP-Dependientes
/
ATPasas Asociadas con Actividades Celulares Diversas
/
GTP Fosfohidrolasas
/
Mitocondrias
Límite:
Humans
Idioma:
En
Revista:
J Cell Sci
Año:
2018
Tipo del documento:
Article
País de afiliación:
Italia