REVERSIBLECOX

Reversibility and tissue specificity of mitochondrial translation defects in early childhood

 Coordinatore UNIVERSITY OF NEWCASTLE UPON TYNE 

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 Nazionalità Coordinatore United Kingdom [UK]
 Totale costo 1˙432˙075 €
 EC contributo 1˙432˙075 €
 Programma FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call ERC-2012-StG_20111109
 Funding Scheme ERC-SG
 Anno di inizio 2013
 Periodo (anno-mese-giorno) 2013-03-01   -   2018-02-28

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    UNIVERSITY OF NEWCASTLE UPON TYNE

 Organization address address: Kensington Terrace 6
city: NEWCASTLE UPON TYNE
postcode: NE1 7RU

contact info
Titolo: Dr.
Nome: Amanda
Cognome: Gregory
Email: send email
Telefono: 441913000000
Fax: 441913000000

UK (NEWCASTLE UPON TYNE) hostInstitution 1˙432˙075.00
2    UNIVERSITY OF NEWCASTLE UPON TYNE

 Organization address address: Kensington Terrace 6
city: NEWCASTLE UPON TYNE
postcode: NE1 7RU

contact info
Titolo: Dr.
Nome: Rita
Cognome: Horvath
Email: send email
Telefono: 441912000000
Fax: 441912000000

UK (NEWCASTLE UPON TYNE) hostInstitution 1˙432˙075.00

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

mtdna    compensatory    trnaglu    mutation    mt    gt    base       cox    recovery    skeletal    onset    showing    reversible    disease    deficiency    life    mitochondrial       complete    homoplasmic    muscle    molecular    patients    syndrome    spontaneous   

 Obiettivo del progetto (Objective)

'We have recently identified the molecular genetic cause of a puzzling clinical syndrome, initially termed “benign infantile mitochondrial myopathy due to reversible cytochrome c oxidase (COX) deficiency”. While childhood-onset mitochondrial encephalomyopathies are usually severe, relentlessly progressive conditions with fatal outcome, this syndrome stands out by showing complete (or almost complete) spontaneous recovery. We have detected the homoplasmic m.14674T>C mutation in the mitochondrial mt-tRNAGlu gene in 17 affected individuals from 12 independent families of different ethnic origins. The m.14674T>C mutation affects the discriminator base of mt-tRNAGlu, the last base at the 3´-end of the molecule, where the amino acid via the terminal CCA is attached, therefore thought to impair mitochondrial translation, as reflected by the COX-negative fibres and the multiple respiratory chain defects in skeletal muscle. The spontaneous recovery of the patients suggests the existence of so far unknown cellular compensatory mechanisms.

We will investigate, i) why patients with reversible COX deficiency show an isolated muscle involvement, ii) why symptoms start uniformly in the first days or weeks of life, iii) what is the molecular basis of the age-dependent, spontaneous recovery, and iv) which factors influence mitochondrial protein synthesis in human cells, skeletal muscle and different tissues. We will study these factors in v) different types of mitochondrial disease.

From a scientific standpoint, this is one of the few hereditary conditions with a life-threatening onset showing recovery. Finding a clearly pathogenic homoplasmic mtDNA mutation offers a new paradigm of mtDNA pathogenesis, and studying this unique disease may unveil factors that are important in other mitochondrial disease. The long-term goal would be to upregulate or boost compensatory factors in patients with mitochondrial disease with the aim to open new avenues for therapy.'

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