CRISTOPA1

Extending the Optic atrophy 1 dependent cristae remodeling: from models to a rationale for therapy of autosomal dominant optic atrophy

Coordinatore	UNIVERSITA DEGLI STUDI DI PADOVA    more  Organization address address: VIA 8 FEBBRAIO 2 city: PADOVA postcode: 35122 contact info Titolo: Dr. Nome: Emanuela Cognome: Pavia Email: send email Telefono: 390498000000 Fax: 390498000000
Nazionalità Coordinatore	Italy [IT]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2013-CIG
Funding Scheme	MC-CIG
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-10-01   -   2017-09-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITA DEGLI STUDI DI PADOVA  Organization address address: VIA 8 FEBBRAIO 2 city: PADOVA postcode: 35122 contact info Titolo: Dr. Nome: Emanuela Cognome: Pavia Email: send email Telefono: 390498000000 Fax: 390498000000	IT (PADOVA)	coordinator	100˙000.00

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 Obiettivo del progetto (Objective)

'Autosomal dominant optic atrophy (ADOA) is caused by mutations in Optic Atrophy 1 (OPA1), a dynamin-related protein of the inner mitochondrial membrane. During the last years, we clarified that OPA1 is a multifunctional protein participating in genetically distinct pathways of mitochondrial fusion and cristae remodelling, both impaired by pathogenetic mutations. We extended our investigation on the (dys)function of OPA1 and our preliminary results indicate that (i) OPA1 is a key modulator of apoptosis and autophagy in vivo; (ii) OPA1 is a master regulator of mitochondrial cristae architecture, impacting on respiratory chain supercomplex assembly and mitochondrial metabolism; (iii) increased autophagy in axons of retinal ganglion cells carrying pathogenic OPA1 depletes them of mitochondria; (iv) OPA1 resides in multimolecular complexes that comprise potential keyregulators of its multiple functions. We therefore hypothesize that by engaging in interactions with different partners, OPA1 regulates mitochondrial functions. Its mutations increase autophagy and susceptibility to apoptosis, especially in RGCs. These multiple regulatory points offer several potential targets for therapeutic strategies that can interfere with the natural course of the disease. In order to verify our hypothesis, we plan to address: (i) how OPA1 regulates mitochondrial metabolism from the cristae; (ii) how changes in OPA1 levels and function impinge on autophagy, especially in RGC; (iii) if the changes in mitochondrial metabolism and autophagy can be exploited therapeutically in vitro and in vivo. This integrated approach aims at unraveling the pathogenesis of ADOA, and therefore to pave the way for its treatment. At the same time, we expect to clarify how mitochondria participate in key cellular metabolic and quality control processes.'