MITOSHAPE

Structural basis of mitochondrial inner membrane shape and dynamic

Coordinatore	MAX-DELBRUCK-CENTRUM FUR MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Germany [DE]
Totale costo	1˙999˙972 €
EC contributo	1˙999˙972 €
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-2013-CoG
Funding Scheme	ERC-CG
Anno di inizio	2014
Periodo (anno-mese-giorno)	2014-07-01   -   2019-06-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	MAX-DELBRUCK-CENTRUM FUR MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT  Organization address address: ROBERT ROSSLE STRASSE 10 city: BERLIN postcode: 13125 contact info Titolo: Dr. Nome: Ioannis Cognome: Legouras Email: send email Telefono: +49 3094064247 Fax: +49 30940649105	DE (BERLIN)	hostInstitution	1˙999˙972.20
2	MAX-DELBRUCK-CENTRUM FUR MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT  Organization address address: ROBERT ROSSLE STRASSE 10 city: BERLIN postcode: 13125 contact info Titolo: Prof. Nome: Oliver Cognome: Daumke Email: send email Telefono: +49 3094063425 Fax: +49 3094062158	DE (BERLIN)	hostInstitution	1˙999˙972.20

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 Obiettivo del progetto (Objective)

'Here, I propose to study the structure and mechanisms of the cellular machineries mediating the shape and dynamics of the mitochondrial inner membrane (IM). The mitochondrial IM contains membrane invaginations called cristae. These are connected by tubular openings, the crista junctions, to the remaining IM. Mitochondrial shape constantly changes due to membrane fission and fusion events, and a balance of both processes is required for proper functioning of mitochondria. Abnormal mitochondrial shape and altered dynamics are associated with severe diseases, such as cancer and neurodegeneration. Sourcing my group’s expertise in dynamin superfamily GTPases, I wish to understand the molecular mechanisms of how OPA1 can achieve mitochondrial IM fusion and cristae formation. To this end, the X-ray crystallographic structure of OPA1 will be determined and complemented by a comprehensive biochemical characterization. Cell-based assays will be employed to decipher the exact mechanism by which OPA1 carries out its two functions and how specific mutations in OPA1 disturb these processes and, thereby, induce human disease. The multiprotein MINOS complex was recently shown to be involved in the formation of crista junctions. I propose to explore the architecture of the MINOS complex. To this end, X-ray crystallographic structures of single components, subcomplexes and, eventually, the complete complex will be determined. Based on these structures, the mechanism of MINOS in mitochondrial membrane remodeling and crista junction formation will be dissected using a structure-based mutagenesis approach. Components of MINOS were shown to interact with OPA1 and with the sorting and assembly machinery (SAM) of the outer mitochondrial membrane. The interactions of MINOS with OPA1 and SAM will be biochemically mapped and structurally characterized. To understand their functions, the effect of disrupting mutations on crista junction formation and mitochondrial dynamics will be explored.'