Human-Specific ARHGAP11B Acts in Mitochondria to Expand Neocortical Progenitors 
by Glutaminolysis.

Namba, Takashi; Dóczi, Judit; Pinson, Anneline; Xing, Lei; Kalebic, Nereo; Wilsch-Bräuninger, Michaela; Long, Katherine S.; Vaid, Samir; Lauer, Janelle; Bogdanova, Aliona; Borgonovo, Barbara; Shevchenko, Anna; Keller, Patrick; Drechsel, David N.; Kurzchalia, Teymuras V.; Wimberger, Pauline; Chinopoulos, Christos; Huttner, Wieland

doi:10.1016/j.neuron.2019.11.027

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Human-Specific ARHGAP11B Acts in Mitochondria to Expand Neocortical Progenitors by Glutaminolysis.

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/persons/resource/persons219479

Namba, Takashi
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons231948

Pinson, Anneline
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons232174

Xing, Lei
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons221457

Kalebic, Nereo
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219790

Wilsch-Bräuninger, Michaela
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons232157

Vaid, Samir
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219372

Lauer, Janelle
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons78966

Bogdanova, Aliona
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219025

Borgonovo, Barbara
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219669

Shevchenko, Anna
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219303

Keller, Patrick
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219118

Drechsel, David N.
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219360

Kurzchalia, Teymuras V.
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219252

Huttner, Wieland
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Citation

Namba, T., Dóczi, J., Pinson, A., Xing, L., Kalebic, N., Wilsch-Bräuninger, M., et al. (2020). Human-Specific ARHGAP11B Acts in Mitochondria to Expand Neocortical Progenitors by Glutaminolysis. Neuron, 105(5), 867-881. doi:10.1016/j.neuron.2019.11.027.

Cite as: https://hdl.handle.net/21.11116/0000-0008-A2C2-5

Abstract

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.