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Scientific article
English

Trichoplein/mitostatin regulates endoplasmic reticulum-mitochondria juxtaposition

Published inEMBO reports, vol. 11, no. 11, p. 854-860
Publication date2010
Abstract

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.

Keywords
  • 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
Citation (ISO format)
CERQUA, Cristina et al. Trichoplein/mitostatin regulates endoplasmic reticulum-mitochondria juxtaposition. In: EMBO reports, 2010, vol. 11, n° 11, p. 854–860. doi: 10.1038/embor.2010.151
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ISSN of the journal1469-221X
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