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The mitochondrial respiratory chain controls intracellular calcium signaling and NFAT activity essential for heart formation in Xenopus laevis.
Chen Y
,
Yuen WH
,
Fu J
,
Huang G
,
Melendez AJ
,
Ibrahim FB
,
Lu H
,
Cao X
.
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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.
Angell,
Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-beta and retinoic acid combination, using a genetic approach.
2000, Pubmed
Angell,
Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-beta and retinoic acid combination, using a genetic approach.
2000,
Pubmed
Berridge,
Calcium signalling: dynamics, homeostasis and remodelling.
2003,
Pubmed
Bezprozvanny,
ATP modulates the function of inositol 1,4,5-trisphosphate-gated channels at two sites.
1993,
Pubmed
Bushdid,
NFATc3 and NFATc4 are required for cardiac development and mitochondrial function.
2003,
Pubmed
Carafoli,
Calcium signaling: a tale for all seasons.
2002,
Pubmed
Chang,
A field of myocardial-endocardial NFAT signaling underlies heart valve morphogenesis.
2004,
Pubmed
Cleaver,
Overexpression of the tinman-related genes XNkx-2.5 and XNkx-2.3 in Xenopus embryos results in myocardial hyperplasia.
1996,
Pubmed
,
Xenbase
Crabtree,
NFAT signaling: choreographing the social lives of cells.
2002,
Pubmed
DiMauro,
Mitochondrial myopathies.
1985,
Pubmed
Duchen,
Mitochondria and calcium: from cell signalling to cell death.
2000,
Pubmed
Dumollard,
Sperm-triggered [Ca2+] oscillations and Ca2+ homeostasis in the mouse egg have an absolute requirement for mitochondrial ATP production.
2004,
Pubmed
Fearnley,
GRIM-19, a cell death regulatory gene product, is a subunit of bovine mitochondrial NADH:ubiquinone oxidoreductase (complex I).
2001,
Pubmed
Fishman,
Fashioning the vertebrate heart: earliest embryonic decisions.
1997,
Pubmed
Graef,
Signals transduced by Ca(2+)/calcineurin and NFATc3/c4 pattern the developing vasculature.
2001,
Pubmed
Hajnóczky,
Decoding of cytosolic calcium oscillations in the mitochondria.
1995,
Pubmed
Harland,
In situ hybridization: an improved whole-mount method for Xenopus embryos.
1991,
Pubmed
,
Xenbase
Hirst,
The nuclear encoded subunits of complex I from bovine heart mitochondria.
2003,
Pubmed
Huang,
GRIM-19, a cell death regulatory protein, is essential for assembly and function of mitochondrial complex I.
2004,
Pubmed
Huang,
Coupling mitochondrial respiratory chain to cell death: an essential role of mitochondrial complex I in the interferon-beta and retinoic acid-induced cancer cell death.
2007,
Pubmed
Komuro,
Csx: a murine homeobox-containing gene specifically expressed in the developing heart.
1993,
Pubmed
Larsson,
Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice.
1998,
Pubmed
Lewis,
Calcium signaling mechanisms in T lymphocytes.
2001,
Pubmed
Lints,
Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants.
1993,
Pubmed
Liu,
Mitochondrial modulation of calcium signaling at the initiation of development.
2001,
Pubmed
Lufei,
GRIM-19, a death-regulatory gene product, suppresses Stat3 activity via functional interaction.
2003,
Pubmed
Lyons,
Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5.
1995,
Pubmed
McCormack,
The role of intramitochondrial Ca2+ in the regulation of oxidative phosphorylation in mammalian tissues.
1993,
Pubmed
Mohun,
The morphology of heart development in Xenopus laevis.
2000,
Pubmed
,
Xenbase
Molkentin,
A calcineurin-dependent transcriptional pathway for cardiac hypertrophy.
1998,
Pubmed
Olson,
Sizing up the heart: development redux in disease.
2003,
Pubmed
Pasumarthi,
Cardiomyocyte cell cycle regulation.
2002,
Pubmed
Putney,
The signal for capacitative calcium entry.
1993,
Pubmed
Rizzuto,
Mitochondria as all-round players of the calcium game.
2000,
Pubmed
Salomon,
Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation.
2001,
Pubmed
Saneyoshi,
The Wnt/calcium pathway activates NF-AT and promotes ventral cell fate in Xenopus embryos.
2002,
Pubmed
,
Xenbase
Schubert,
Requirement of transcription factor NFAT in developing atrial myocardium.
2003,
Pubmed
Schultz,
Structures and proton-pumping strategies of mitochondrial respiratory enzymes.
2001,
Pubmed
Tanaka,
The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development.
1999,
Pubmed
,
Xenbase
Timmerman,
Rapid shuttling of NF-AT in discrimination of Ca2+ signals and immunosuppression.
1996,
Pubmed
Wallace,
Mitochondrial diseases in man and mouse.
1999,
Pubmed
de la Pompa,
Role of the NF-ATc transcription factor in morphogenesis of cardiac valves and septum.
1998,
Pubmed
