The mitochondrial respiratory signaling and NFAT activity chain controls intracellular calcium essential for heart formation in Xenopus laevis

Chen, Y., Yuen, W. H., Fu, J., Huang, G., Melendez, A. J., Ibrahim, F. B. M., Lu, H. and Cao, X. (2007) The mitochondrial respiratory signaling and NFAT activity chain controls intracellular calcium essential for heart formation in Xenopus laevis. Molecular and Cellular Biology, 27(18), pp. 6420-6432. (doi:10.1128/MCB.01946-06)

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Publisher's URL: http://dx.doi.org/10.1128/MCB.01946-06

Abstract

The mitochondrial respiratory chain (MRC) plays crucial roles in cellular energy production. However, its function in early embryonic development remains largely unknown. To address this issue, GRIM-19, a newly identified MRC complex I subunit, was knocked down in Xenopus laevis embryos. A severe deficiency in heart formation was observed, and the deficiency could be rescued by reintroducing human GRIM-19 mRNA. The mechanism involved was further investigated. We found that the activity of NFAT, a transcription factor family that contributes to early organ development, was downregulated in GRIM-19 knockdown embryos. Furthermore, the expression of a constitutively active form of mouse NFATc4 in these embryos rescued the heart developmental defects. NFAT activity is controlled by a calcium-dependent protein phosphatase, calcineurin, which suggests that calcium signaling may be disrupted by GRIM-19 knockdown. Indeed, both the calcium response and calcium-induced NFAT activity were impaired in the GRIM-19 or NDUFS3 (another complex I subunit) knockdown cell lines. We also showed that NFAT can rescue expression of Nkx2.5, which is one of the key genes for early heart development. Our data demonstrated the essential role of MRC in heart formation and revealed the signal transduction and gene expression cascade involved in this process.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Melendez Romero, Dr Alirio
Authors: Chen, Y., Yuen, W. H., Fu, J., Huang, G., Melendez, A. J., Ibrahim, F. B. M., Lu, H., and Cao, X.
College/School:College of Medical Veterinary and Life Sciences
Journal Name:Molecular and Cellular Biology
Publisher:American Society for Microbiology
ISSN:0270-7306
ISSN (Online):1098-5549
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
462311Therapeutic potential of Sphingosine Kinase blockage in allergic anaphylaxis.Alirio Melendez RomeroMedical Research Council (MRC)G0700794Institute of Infection Immunity and Inflammation