MITO BY-PASS

Molecular by-pass therapy for mitochondrial dysfunction

Coordinatore	TAMPEREEN YLIOPISTO    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Finland [FI]
Totale costo	2˙436˙000 €
EC contributo	2˙436˙000 €
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-2008-AdG
Funding Scheme	ERC-AG
Anno di inizio	2009
Periodo (anno-mese-giorno)	2009-04-01   -   2015-03-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	HELSINGIN YLIOPISTO  Organization address address: YLIOPISTONKATU 4 city: HELSINGIN YLIOPISTO postcode: 14 contact info Titolo: Mrs. Nome: Tiina Cognome: Berg Email: send email Telefono: +358 9 19125129	FI (HELSINGIN YLIOPISTO)	beneficiary	785˙213.00
2	TAMPEREEN YLIOPISTO  Organization address address: Kalevantie 4 city: TAMPERE postcode: 33014 contact info Titolo: Ms. Nome: Hannele Cognome: Auffermann Email: send email Telefono: +358 3 355111 Fax: +358 3 2134473	FI (TAMPERE)	hostInstitution	1˙650˙787.00
3	TAMPEREEN YLIOPISTO  Organization address address: Kalevantie 4 city: TAMPERE postcode: 33014 contact info Titolo: Prof. Nome: Howard Trevor Cognome: Jacobs Email: send email Telefono: 358336000000 Fax: 358336000000	FI (TAMPERE)	hostInstitution	1˙650˙787.00

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 Obiettivo del progetto (Objective)

'Many eukaryotes, but not the higher metazoans such as vertebrates or arthropods, possess intrinsic by-pass systems that provide alternative routes for electron flow from NADH to oxygen. Whereas the standard mitochondrial OXPHOS system couples electron transport to proton pumping across the inner mitochondrial membrane, creating the proton gradient which is used to drive ATP synthesis and other energy-requiring processes, the by-pass enzymes are non-proton-pumping, and their activity is redox-regulated rather than subject to ATP requirements. My laboratory has engineered two of these by-pass enzymes, the single-subunit NADH dehydrogenase Ndi1p from yeast, and the alternative oxidase AOX from Ciona intestinalis, for expression in Drosophila and mammalian cells. Their expression is benign, and the enzymes appear to be almost inert, except under conditions of redox stress induced by OXPHOS toxins or mutations. The research set out in this proposal will explore the utility of these by-passes for alleviating metabolic stress in the whole organism and in specific tissues, arising from mitochondrial OXPHOS dysfunction. Specifically, I will test the ability of Ndi1p and AOX in Drosophila and in mammalian models to compensate for the toxicity of OXPHOS poisons, to complement disease-equivalent mutations impairing the assembly or function of the OXPHOS system, and to diminish the pathological excess production of reactive oxygen species seen in many neurodegenerative disorders associated with OXPHOS impairment, and under conditions of ischemia-reperfusion. The attenuation of endogenous mitochondrial ROS production by deployment of these by-pass enzymes also offers a novel route to testing the mitochondrial (oxyradical) theory of ageing.'