MDS · The Molecular Basis of Mitochondrial Disease: Elucidating the Function of the Mitochondrial Inner Membrane Protein MPV17
FP7 — People (Marie Curie Actions)
- Duration
- 2010-05-01 → 2012-04-30
- EU contribution
- €231,427
- Participants
- 1
- Scheme
- MC-IEF
Lines connect the coordinator with its partners.
Results in brief
The Molecular Basis of Mitochondrial Disease: Elucidating the Function of the Mitochondrial Inner Membrane Protein MPV17
Mitochondria generate energy for the cell, and to do so requires the protein products of a small piece of DNA (mitochondrial DNA, or mtDNA), which it harbours, as well as many proteins from the nucleus. One nuclear gene called MPV17 is needed to help maintain mtDNA, we know this because Dr Spinazzola discovered that mutations in MPV17 are responsible for a human disease which results in mitochondrial DNA depletion syndrome (MDS). The primary research aim of the fellowship was to understand the function of MPV17, thereby aiding the design of rational therapies for MPV17 deficiency and potentially also other forms of MDS. At the inception of the project, neither the function of MPV17, nor the mechanism leading to mtDNA depletion was known.
Data: CORDIS, © European Union
Project objective
Mitochondria contain their own DNA (mtDNA), which contributes essential components of the energy generating system of the organelle. Because mtDNA requires many nuclear gene products for its maintenance and expression, nuclear gene defects can lead to mtDNA loss. MPV17 is one such gene, pathological mutations in MPV17 were identified by the researcher as a cause of mtDNA loss, yet the function of the protein remains obscure. The primary aim of the project is to elucidate the function of MPV17p, in order to understand how mutations in this gene cause mtDNA loss and human pathology. Specific aims are: i) to affinity-purify tagged versions of MPV17p from human cultured cells with the aim of identifying partner proteins. ii) To characterize the protein components of the different molecular weight complexes that contain MPV17p, using native electrophoresis. iii) To determine the effects of modulating the expression of MPV17p upon mitochondrial function and mtDNA integrity and stability in human cells, using an inducible expression system. iv) To harvest correctly folded and functional recombinant MPV17p from bacterial membranes for in vitro experiments and structural biology studies. The new information is expected to provide further insights into mitochondrial diseases and to yield fundamental knowledge of the mitochondrion. It is anticipated that the advance in knowledge will have implications for disorders of mitochondrial DNA maintenance in general, not only those related directly to mutations in MPV17.
Original text from CORDIS.
Participants
- MEDICAL RESEARCH COUNCIL · LONDONCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union