Reference : Human-Specific ARHGAP11B Acts in Mitochondria to Expand Neocortical Progenitors by Gl...
Scientific journals : Article
Human health sciences : Neurology
http://hdl.handle.net/2268/255222
Human-Specific ARHGAP11B Acts in Mitochondria to Expand Neocortical Progenitors by Glutaminolysis.
English
Namba, Takashi [> >]
Dóczi, Judit [> >]
Pinson, Anneline mailto [Université de Liège - ULiège > > >]
Xing, Lei [> >]
Kalebic, Nereo [> >]
Wilsch-Bräuninger, Michaela [> >]
Long, Katherine R. [> >]
Vaid, Samir [> >]
Lauer, Janelle [> >]
Bogdanova, Aliona [> >]
Borgonovo, Barbara [> >]
Shevchenko, Anna [> >]
Keller, Patrick [> >]
Drechsel, David [> >]
Kurzchalia, Teymuras [> >]
Wimberger, Pauline [> >]
Chinopoulos, Christos [> >]
Huttner, Wieland B. [> >]
2020
Neuron
105
5
867-881.e9
Yes (verified by ORBi)
08966273
10974199
United States
[en] 3T3 Cells ; Animals ; Biological Evolution ; Cell Proliferation/genetics ; Citric Acid Cycle ; GTPase-Activating Proteins/genetics/metabolism ; Gene Expression Regulation, Developmental/genetics ; Glutamic Acid/metabolism ; Glutamine/metabolism ; Humans ; Mice ; Mitochondria/metabolism ; Mitochondrial ADP, ATP Translocases/metabolism ; Mitochondrial Membrane Transport Proteins/metabolism ; Mitochondrial Permeability Transition Pore ; Neocortex/embryology/metabolism ; Neural Stem Cells/metabolism ; Neurogenesis/genetics ; evolution ; metabolism ; neocortex ; neural progenitor cells
[en] The human-specific gene ARHGAP11B is preferentially expressed in neural progenitors of fetal human neocortex and increases abundance and proliferation of basal progenitors (BPs), which have a key role in neocortex expansion. ARHGAP11B has therefore been implicated in the evolutionary expansion of the human neocortex, but its mode of action has been unknown. Here, we show that ARHGAP11B is imported into mitochondria, where it interacts with the adenine nucleotide translocase (ANT) and inhibits the mitochondrial permeability transition pore (mPTP). BP expansion by ARHGAP11B requires its presence in mitochondria, and pharmacological inhibition of ANT function or mPTP opening mimic BP expansion by ARHGAP11B. Searching for the underlying metabolic basis, we find that BP expansion by ARHGAP11B requires glutaminolysis, the conversion of glutamine to glutamate for the tricarboxylic acid (TCA) cycle. Hence, an ARHGAP11B-induced, mitochondria-based effect on BP metabolism that is a hallmark of highly mitotically active cells appears to underlie its role in neocortex expansion.
http://hdl.handle.net/2268/255222
Copyright © 2019 Elsevier Inc. All rights reserved.

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