MitoNEET-dependent formation of intermitochondrial junctions

Alexandre Vernay, Anna Marchetti, Ayman Sabra, Tania N. Jauslin, Manon Rosselin, Philipp E. Scherer, Nicolas Demaurex, Lelio Orci, Pierre Cosson

Research output: Contribution to journalArticle

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Abstract

MitoNEET (mNEET) is a dimeric mitochondrial outer membrane protein implicated in many facets of human pathophysiology, notably diabetes and cancer, but its molecular function remains poorly characterized. In this study, we generated and analyzed mNEET KO cells and found that in these cells the mitochondrial network was disturbed. Analysis of 3D-EM reconstructions and of thin sections revealed that genetic inactivation of mNEET did not affect the size of mitochondria but that the frequency of intermitochondrial junctions was reduced. Loss of mNEET decreased cellular respiration, because of a reduction in the total cellular mitochondrial volume, suggesting that intermitochondrial contacts stabilize individual mitochondria. Reexpression of mNEET in mNEET KO cells restored the WT morphology of the mitochondrial network, and reexpression of a mutant mNEET resistant to oxidative stress increased in addition the resistance of the mitochondrial network to H2O2-induced fragmentation. Finally, overexpression of mNEET increased strongly intermitochondrial contacts and resulted in the clustering of mitochondria. Our results suggest that mNEET plays a specific role in the formation of intermitochondrial junctions and thus participates in the adaptation of cells to physiological changes and to the control of mitochondrial homeostasis.

Original languageEnglish (US)
Pages (from-to)8277-8282
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number31
DOIs
StatePublished - Aug 1 2017

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Mitochondrial Size
Mitochondria
Cell Respiration
Cluster Analysis
Membrane Proteins
Oxidative Stress
Homeostasis
Neoplasms

Keywords

  • CISD1
  • Endoplasmic reticulum
  • Intermitochondrial junctions
  • Mitochondria
  • MitoNEET

ASJC Scopus subject areas

  • General

Cite this

MitoNEET-dependent formation of intermitochondrial junctions. / Vernay, Alexandre; Marchetti, Anna; Sabra, Ayman; Jauslin, Tania N.; Rosselin, Manon; Scherer, Philipp E.; Demaurex, Nicolas; Orci, Lelio; Cosson, Pierre.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 31, 01.08.2017, p. 8277-8282.

Research output: Contribution to journalArticle

Vernay, A, Marchetti, A, Sabra, A, Jauslin, TN, Rosselin, M, Scherer, PE, Demaurex, N, Orci, L & Cosson, P 2017, 'MitoNEET-dependent formation of intermitochondrial junctions', Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 31, pp. 8277-8282. https://doi.org/10.1073/pnas.1706643114
Vernay, Alexandre ; Marchetti, Anna ; Sabra, Ayman ; Jauslin, Tania N. ; Rosselin, Manon ; Scherer, Philipp E. ; Demaurex, Nicolas ; Orci, Lelio ; Cosson, Pierre. / MitoNEET-dependent formation of intermitochondrial junctions. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 31. pp. 8277-8282.
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