MitoNEET-dependent formation of intermitochondrial junctions

作者：Vernay Alexandre; Marchetti Anna; Sabra Ayman; Jauslin Tania N; Rosselin Manon; Scherer Philipp E; Demaurex Nicolas; Orci Lelio^*; Cosson Pierre^*

来源：Proceedings of the National Academy of Sciences, 2017, 114(31): 8277-8282.

DOI：10.1073/pnas.1706643114

• mitoNEET
• CISD1
• mitochondria
• intermitochondrial junctions
• endoplasmic reticulum

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.

• 出版日期2017-8-1