Trichoplein/mitostatin regulates endoplasmic reticulum-mitochondria juxtaposition

Article Article scientifique Article Trichoplein/mitostatin regulates endoplasmic reticulum-mitochondria juxtaposition eng 2010 author Cerqua Cristina author Anesti Vassiliki author Pyakurel Aswin 668691 author Liu Dan 682919 author Naon Deborah author Wiche Gerhard author Baffa Raffaele author Dimmer Kai S. author Scorrano Luca 659421 854-860 10.1038/embor.2010.151 20930847 1469-221X http://www.nature.com/embor/journal/v11/n11/pdf/embor2010151.pdf Trichoplein/mitostatin (TpMs) is a keratin-binding protein that partly colocalizes with mitochondria and is often downregulated in epithelial cancers, but its function remains unclear. In this study, we report that TpMs regulates the tethering between mitochondria and endoplasmic reticulum (ER) in a Mitofusin 2 (Mfn2)-dependent manner. Subcellular fractionation and immunostaining show that TpMs is present at the interface between mitochondria and ER. The expression of TpMs leads to mitochondrial fragmentation and loosens tethering with ER, whereas its silencing has opposite effects. Functionally, the reduced tethering by TpMs inhibits apoptosis by Ca(2+)-dependent stimuli that require ER-mitochondria juxtaposition. Biochemical and genetic evidence support a model in which TpMs requires Mfn2 to modulate mitochondrial shape and tethering. Thus, TpMs is a new regulator of mitochondria-ER juxtaposition. Animals Calcium/pharmacology Carrier Proteins/*metabolism Cell Death/drug effects Endoplasmic Reticulum/drug effects/*metabolism GTP Phosphohydrolases/metabolism HeLa Cells Humans Membrane Proteins/metabolism Mice Mitochondria/drug effects/*metabolism Mitochondrial Proteins/metabolism Organelle Shape/drug effects Protein Binding/drug effects Protein Transport/drug effects Tumor Suppressor Proteins/*metabolism Dewey 612 134 Département de physiologie cellulaire et métabolisme 21C false 512 Les mitochondries dans la vie cellulaire 850 EMBO reports 11 11 73b557fa-b5a2-4dc3-9b69-ae1a32511cde Article Restricted file1.pdf 1357619 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme

Title	Published in	Year	Views	Downloads

Trichoplein/mitostatin regulates endoplasmic reticulum-mitochondria juxtaposition	EMBO reports	2010	583	0
The SUMO arena goes mitochondrial with MAPL	EMBO reports	2009	523	0

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