RGD Reference Report - Mitochondrial fission is required for cardiomyocyte hypertrophy mediated by a Ca2+-calcineurin signaling pathway. - Rat Genome Database

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Mitochondrial fission is required for cardiomyocyte hypertrophy mediated by a Ca2+-calcineurin signaling pathway.

Authors: Pennanen, Christian  Parra, Valentina  López-Crisosto, Camila  Morales, Pablo E  Del Campo, Andrea  Gutierrez, Tomás  Rivera-Mejías, Pablo  Kuzmicic, Jovan  Chiong, Mario  Zorzano, Antonio  Rothermel, Beverly A  Lavandero, Sergio 
Citation: Pennanen C, etal., J Cell Sci. 2014 Jun 15;127(Pt 12):2659-71. doi: 10.1242/jcs.139394. Epub 2014 Apr 28.
RGD ID: 13204833
Pubmed: PMID:24777478   (View Abstract at PubMed)
PMCID: PMC4058110   (View Article at PubMed Central)
DOI: DOI:10.1242/jcs.139394   (Journal Full-text)

Cardiomyocyte hypertrophy has been associated with diminished mitochondrial metabolism. Mitochondria are crucial organelles for the production of ATP, and their morphology and function are regulated by the dynamic processes of fusion and fission. The relationship between mitochondrial dynamics and cardiomyocyte hypertrophy is still poorly understood. Here, we show that treatment of cultured neonatal rat cardiomyocytes with the hypertrophic agonist norepinephrine promotes mitochondrial fission (characterized by a decrease in mitochondrial mean volume and an increase in the relative number of mitochondria per cell) and a decrease in mitochondrial function. We demonstrate that norepinephrine acts through α1-adrenergic receptors to increase cytoplasmic Ca(2+), activating calcineurin and promoting migration of the fission protein Drp1 (encoded by Dnml1) to mitochondria. Dominant-negative Drp1 (K38A) not only prevented mitochondrial fission, it also blocked hypertrophic growth of cardiomyocytes in response to norepinephrine. Remarkably, an antisense adenovirus against the fusion protein Mfn2 (AsMfn2) was sufficient to increase mitochondrial fission and stimulate a hypertrophic response without agonist treatment. Collectively, these results demonstrate the importance of mitochondrial dynamics in the development of cardiomyocyte hypertrophy and metabolic remodeling.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of sarcomere organization  IMP 13204833 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mfn2  (mitofusin 2)


Additional Information