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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
- natural sciences chemical sciences organic chemistry amines
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2012-StG_20111109
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Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Host institution
NE1 7RU Newcastle Upon Tyne
United Kingdom
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