Cell Metabolic Alterations due to Mcph1 Mutation in Microcephaly

Nathalie Journiac; Javier Gilabert-Juan; Sara Cipriani; Paule Benit; Xiaoqian Liu; Sandrine Jacquier; Valérie Faivre; Andrée Delahaye-Duriez; Zsolt Csaba; Tristan Hourcade; Eliza Melinte; Sophie Lebon; Céline Violle-Poirsier; Jean-François Oury; Homa Adle-Biassette; Zhao-Qi Wang; Shyamala Mani; Pierre Rustin; Pierre Gressens; Jeannette Nardelli

doi:10.1016/j.celrep.2020.03.070

Cell Metabolic Alterations due to Mcph1 Mutation in Microcephaly

Nathalie Journiac, Javier Gilabert-Juan, Sara Cipriani, Paule Benit, Xiaoqian Liu, Sandrine Jacquier, Valérie Faivre, Andrée Delahaye-Duriez, Zsolt Csaba, Tristan Hourcade, Eliza Melinte, Sophie Lebon, Céline Violle-Poirsier, Jean-François Oury, Homa Adle-Biassette, Zhao-Qi Wang, Shyamala Mani, Pierre Rustin, Pierre Gressens, Jeannette Nardelli

University of Paris VII - Denis Diderot University
Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany.
Université de Paris, NeuroDiderot, Inserm, 75019 Paris, France; Service d'Histologie, Embryologie, et Cytogénétique, Hôpital Jean Verdier, Saint Denis, AP-HP, Université Paris 13, Sorbonne Paris Cité, Bobigny, France.
Service de Génétique et Biologie de la Reproduction, CHU Reims, Reims, France.
Université de Paris, NeuroDiderot, Inserm, 75019 Paris, France; Service d'Anatomie et de Cytologie Pathologiques, Hôpital Lariboisière, AP-HP, Paris, France.
Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany; Faculty of Biology and Pharmacy, Friedrich-Schiller University of Jena, Jena, Germany.
Université de Paris, NeuroDiderot, Inserm, 75019 Paris, France; Curadev Pharma Pvt. Ltd., Noida, India.
Université de Paris, NeuroDiderot, Inserm, 75019 Paris, France; Centre for the Developing Brain, Department of Perinatal Imaging and Health, Division of Imaging, Sciences and Biochemical Engineering, King's College London, St. Thomas' Hospital, London, UK. Electronic address: pierre.gressens@inserm.fr.
Université de Paris, NeuroDiderot, Inserm, 75019 Paris, France. Electronic address: jeannette.nardelli@inserm.fr.

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Abstract

A distinctive feature of neocortical development is the highly coordinated production of different progenitor cell subtypes, which are critical for ensuring adequate neurogenic outcome and the development of normal neocortical size. To further understand the mechanisms that underlie neocortical growth, we focused our studies on the microcephaly gene Mcph1, and we report here that Mcph1 (1) exerts its functions in rapidly dividing apical radial glial cells (aRGCs) during mouse neocortical development stages that precede indirect neurogenesis; (2) is expressed at mitochondria; and (3) controls the proper proliferation and survival of RGCs, potentially through crosstalk with cellular metabolic pathways involving the stimulation of mitochondrial activity via VDAC1/GRP75 and AKT/HK2/VDAC1 and glutaminolysis via ATF4/PCK2. We currently report the description of a MCPH-gene implication in the interplay between bioenergetic pathways and neocortical growth, thus pointing to alterations of cellular metabolic pathways, in particular glutaminolysis, as a possible cause of microcephalic pathogenesis.

Original language	English
Article number	107506
Journal	Cell Reports
Volume	31
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2020.03.070
Publication status	Published - 14 Apr 2020

Keywords

ATF4
GRP75
PCK2
VDAC1

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10.1016/j.celrep.2020.03.070

Journiac-CellRep-20Final published version, 9.5 MBLicence: CC BY-NC-ND
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Journiac, N., Gilabert-Juan, J., Cipriani, S., Benit, P., Liu, X., Jacquier, S., Faivre, V., Delahaye-Duriez, A., Csaba, Z., Hourcade, T., Melinte, E., Lebon, S., Violle-Poirsier, C., Oury, J-F., Adle-Biassette, H., Wang, Z-Q., Mani, S., Rustin, P., Gressens, P., & Nardelli, J. (2020). Cell Metabolic Alterations due to Mcph1 Mutation in Microcephaly. Cell Reports, 31(2), [107506]. https://doi.org/10.1016/j.celrep.2020.03.070

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title = "Cell Metabolic Alterations due to Mcph1 Mutation in Microcephaly",

abstract = "A distinctive feature of neocortical development is the highly coordinated production of different progenitor cell subtypes, which are critical for ensuring adequate neurogenic outcome and the development of normal neocortical size. To further understand the mechanisms that underlie neocortical growth, we focused our studies on the microcephaly gene Mcph1, and we report here that Mcph1 (1) exerts its functions in rapidly dividing apical radial glial cells (aRGCs) during mouse neocortical development stages that precede indirect neurogenesis; (2) is expressed at mitochondria; and (3) controls the proper proliferation and survival of RGCs, potentially through crosstalk with cellular metabolic pathways involving the stimulation of mitochondrial activity via VDAC1/GRP75 and AKT/HK2/VDAC1 and glutaminolysis via ATF4/PCK2. We currently report the description of a MCPH-gene implication in the interplay between bioenergetic pathways and neocortical growth, thus pointing to alterations of cellular metabolic pathways, in particular glutaminolysis, as a possible cause of microcephalic pathogenesis.",

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author = "Nathalie Journiac and Javier Gilabert-Juan and Sara Cipriani and Paule Benit and Xiaoqian Liu and Sandrine Jacquier and Val{\'e}rie Faivre and Andr{\'e}e Delahaye-Duriez and Zsolt Csaba and Tristan Hourcade and Eliza Melinte and Sophie Lebon and C{\'e}line Violle-Poirsier and Jean-Fran{\c c}ois Oury and Homa Adle-Biassette and Zhao-Qi Wang and Shyamala Mani and Pierre Rustin and Pierre Gressens and Jeannette Nardelli",

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Journiac, N, Gilabert-Juan, J, Cipriani, S, Benit, P, Liu, X, Jacquier, S, Faivre, V, Delahaye-Duriez, A, Csaba, Z, Hourcade, T, Melinte, E, Lebon, S, Violle-Poirsier, C, Oury, J-F, Adle-Biassette, H, Wang, Z-Q, Mani, S, Rustin, P, Gressens, P & Nardelli, J 2020, 'Cell Metabolic Alterations due to Mcph1 Mutation in Microcephaly', Cell Reports, vol. 31, no. 2, 107506. https://doi.org/10.1016/j.celrep.2020.03.070

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T1 - Cell Metabolic Alterations due to Mcph1 Mutation in Microcephaly

AU - Journiac, Nathalie

AU - Gilabert-Juan, Javier

AU - Cipriani, Sara

AU - Benit, Paule

AU - Liu, Xiaoqian

AU - Jacquier, Sandrine

AU - Faivre, Valérie

AU - Delahaye-Duriez, Andrée

AU - Csaba, Zsolt

AU - Hourcade, Tristan

AU - Melinte, Eliza

AU - Lebon, Sophie

AU - Violle-Poirsier, Céline

AU - Oury, Jean-François

AU - Adle-Biassette, Homa

AU - Wang, Zhao-Qi

AU - Mani, Shyamala

AU - Rustin, Pierre

AU - Gressens, Pierre

AU - Nardelli, Jeannette

PY - 2020/4/14

Y1 - 2020/4/14

N2 - A distinctive feature of neocortical development is the highly coordinated production of different progenitor cell subtypes, which are critical for ensuring adequate neurogenic outcome and the development of normal neocortical size. To further understand the mechanisms that underlie neocortical growth, we focused our studies on the microcephaly gene Mcph1, and we report here that Mcph1 (1) exerts its functions in rapidly dividing apical radial glial cells (aRGCs) during mouse neocortical development stages that precede indirect neurogenesis; (2) is expressed at mitochondria; and (3) controls the proper proliferation and survival of RGCs, potentially through crosstalk with cellular metabolic pathways involving the stimulation of mitochondrial activity via VDAC1/GRP75 and AKT/HK2/VDAC1 and glutaminolysis via ATF4/PCK2. We currently report the description of a MCPH-gene implication in the interplay between bioenergetic pathways and neocortical growth, thus pointing to alterations of cellular metabolic pathways, in particular glutaminolysis, as a possible cause of microcephalic pathogenesis.

AB - A distinctive feature of neocortical development is the highly coordinated production of different progenitor cell subtypes, which are critical for ensuring adequate neurogenic outcome and the development of normal neocortical size. To further understand the mechanisms that underlie neocortical growth, we focused our studies on the microcephaly gene Mcph1, and we report here that Mcph1 (1) exerts its functions in rapidly dividing apical radial glial cells (aRGCs) during mouse neocortical development stages that precede indirect neurogenesis; (2) is expressed at mitochondria; and (3) controls the proper proliferation and survival of RGCs, potentially through crosstalk with cellular metabolic pathways involving the stimulation of mitochondrial activity via VDAC1/GRP75 and AKT/HK2/VDAC1 and glutaminolysis via ATF4/PCK2. We currently report the description of a MCPH-gene implication in the interplay between bioenergetic pathways and neocortical growth, thus pointing to alterations of cellular metabolic pathways, in particular glutaminolysis, as a possible cause of microcephalic pathogenesis.

KW - ATF4

KW - GRP75

KW - PCK2

KW - VDAC1

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U2 - 10.1016/j.celrep.2020.03.070

DO - 10.1016/j.celrep.2020.03.070

M3 - Article

C2 - 32294449

SN - 2211-1247

VL - 31

JO - Cell Reports

JF - Cell Reports

IS - 2

M1 - 107506

ER -

Cell Metabolic Alterations due to Mcph1 Mutation in Microcephaly

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Keywords

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