Objective Organelles are not randomly organized in the cytoplasm of the cell, but often are orderly arranged in mutual relationships that depend on physical, protein bounds. Understanding the molecular nature of the tethers that regulate relative position and juxtaposition of the organelles is one of the main quests of cell biology, given their functional importance. For example, the juxtaposition between mitochondria and endoplasmic reticulum (ER) has been suggested by us and others to crucially impact on Ca2+ signalling and apoptosis. We recently identified the first structural ER-mitochondrial tether in mitofusin 2 (Mfn2), a pro-fusion mitochondria-shaping protein. A fraction of Mfn2 is also located on the ER regulating its morphology, and acting in trans to tether it to mitochondria. The tethering function of Mfn2 impacts on the transmission of Ca2+ signals between the two organelles and is regulated by the oncosuppressor trichoplein/mitostatin. Mfn2 is likely only one of the tethers, as others exist in yeast. Furthermore, the dynamicity of the ER-mitochondria contact is known, but remains poorly understood. Therefore, a clear picture of the anatomy and pathophsyiology of ER-mitochondrial connection is far from being reached.Here we hypothesize that ER-mitochondrial contacts are crucial specialized hubs of cellular signalling whose architecture is modulated by cellular cues, impacting on integrated signalling cascades and ultimately affecting cellular function. To address this hypothesis we wish to setup a research project that aims at (i) increasing our knowledge on the molecular nature of tethers and modulators of ER-mitochondrial tethers in mammalian cells; (ii) clarifying how mitochondrial and ER function are controlled by the tethering; (iii) addressing how juxtaposition influences complex cellular responses including autophagy and cell death; (iv) elucidating the role of tethering in vivo by generating animal models with defined ER-mitochondrial distance. Fields of science medical and health sciencesbasic medicinephysiologypathophysiologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencescell biology Programme(s) 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) Topic(s) ERC-SG-LS3 - ERC Starting Grant - Cellular and Developmental Biology Call for proposal ERC-2011-StG_20101109 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Coordinator UNIVERSITA DEGLI STUDI DI PADOVA Address Via 8 febbraio 2 35122 Padova Italy See on map Region Nord-Est Veneto Padova Activity type Higher or Secondary Education Establishments Administrative Contact Gerolamo Lanfranchi (Prof.) Principal investigator Luca Scorrano (Prof.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data Beneficiaries (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSITA DEGLI STUDI DI PADOVA Italy EU contribution € 1 157 633,32 Address Via 8 febbraio 2 35122 Padova See on map Region Nord-Est Veneto Padova Activity type Higher or Secondary Education Establishments Administrative Contact Gerolamo Lanfranchi (Prof.) Principal investigator Luca Scorrano (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data UNIVERSITE DE GENEVE Participation ended Switzerland EU contribution € 342 361,88 Address Rue du general dufour 24 1211 Geneve See on map Region Schweiz/Suisse/Svizzera Région lémanique Genève Activity type Higher or Secondary Education Establishments Administrative Contact Alex Waehry (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data
