title: New roles for OMA1 metalloprotease: From mitochondrial proteostasis to metabolic homeostasis.
abstract: The mitochondrial quality control system is essential for the preservation and regulation of mitochondrial function. This system is formed by a complex machinery that controls and maintains protein function and regulates mitochondrial morphology through a coordinated system of continual fusion and fission events. Impairments in the mitochondrial quality control system through either mutation or deficiency in any of its components, can lead to mitochondrial dysfunction. However, the physiological consequences of these deficiencies remain unknown in most cases. Here, we briefly review the role of the OPA1-OMA1 system in mitochondrial biology, and summarize our recent report on the generation and phenotypic characterization of a model deficient in OMA1, an ATP-independent mitochondrial metalloprotease that participates in mitochondrial quality control. Interestingly,Oma1-deficient mice display an obesity phenotype, characterized by hepatic steatosis, decrease in energy expenditure and defective thermogenic regulation. In addition, our study has provided in vivo evidence of OMA1 function as a mitochondrial quality control protease, inactivating OPA1 under stress conditions and inhibiting mitochondrial fusion. Further, we have demonstrated the essential role of the OMA1-OPA1 system for brown adipose function and how this system regulates metabolic homeostasis in mice.
authors.affiliation: Departamento de Bioquímica y Biología Molecular; Facultad de Medicina; Instituto Universitario de Oncología; Universidad de Oviedo; Oviedo, Spain.
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Quirós
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ramsay
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Otín
keywords: brown adipose tissue; mitochondrial dynamics; obesity; protease