RGD Reference Report - Loss of mitochondrial protease OMA1 alters processing of the GTPase OPA1 and causes obesity and defective thermogenesis in mice. - Rat Genome Database

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Loss of mitochondrial protease OMA1 alters processing of the GTPase OPA1 and causes obesity and defective thermogenesis in mice.

Authors: Quirós, Pedro M  Ramsay, Andrew J  Sala, David  Fernández-Vizarra, Erika  Rodríguez, Francisco  Peinado, Juan R  Fernández-García, Maria Soledad  Vega, José A  Enríquez, José A  Zorzano, Antonio  López-Otín, Carlos 
Citation: Quirós PM, etal., EMBO J. 2012 May 2;31(9):2117-33. doi: 10.1038/emboj.2012.70. Epub 2012 Mar 20.
RGD ID: 13673832
Pubmed: PMID:22433842   (View Abstract at PubMed)
PMCID: PMC3343468   (View Article at PubMed Central)
DOI: DOI:10.1038/emboj.2012.70   (Journal Full-text)

Mitochondria are dynamic subcellular organelles that convert nutrient intermediates into readily available energy equivalents. Optimal mitochondrial function is ensured by a highly evolved quality control system, coordinated by protein machinery that regulates a process of continual fusion and fission. In this work, we provide in vivo evidence that the ATP-independent metalloprotease OMA1 plays an essential role in the proteolytic inactivation of the dynamin-related GTPase OPA1 (optic atrophy 1). We also show that OMA1 deficiency causes a profound perturbation of the mitochondrial fusion-fission equilibrium that has important implications for metabolic homeostasis. Thus, ablation of OMA1 in mice results in marked transcriptional changes in genes of lipid and glucose metabolic pathways and substantial alterations in circulating blood parameters. Additionally, Oma1-mutant mice exhibit an increase in body weight due to increased adipose mass, hepatic steatosis, decreased energy expenditure and impaired thermogenenesis. These alterations are especially significant under metabolic stress conditions, indicating that an intact OMA1-OPA1 system is essential for developing the appropriate adaptive response to different metabolic stressors such as a high-fat diet or cold-shock. This study provides the first description of an unexpected role in energy metabolism for the metalloprotease OMA1 and reinforces the importance of mitochondrial quality control for normal metabolic function.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of cold-induced thermogenesis involved_inISSUniProtKB:Q9D8H713673832PMID:22433842YuBioLab 

Objects Annotated

Genes (Rattus norvegicus)
Oma1  (OMA1 zinc metallopeptidase)


Additional Information