Cell Metabolic Alterations due to Mcph1 Mutation in Microcephaly.
Animals
Cell Cycle Proteins
/ genetics
Cell Differentiation
/ genetics
Cell Proliferation
/ genetics
Cell Survival
/ genetics
Cytoskeletal Proteins
/ genetics
Female
HEK293 Cells
HSP70 Heat-Shock Proteins
/ genetics
Humans
Male
Mice
Mice, Inbred C57BL
Microcephaly
/ genetics
Mitochondria
/ metabolism
Mitochondrial Proteins
/ genetics
Mutation
Nerve Tissue Proteins
/ metabolism
Neurogenesis
/ genetics
Neuroglia
/ metabolism
Neurons
/ metabolism
Voltage-Dependent Anion Channel 1
/ genetics
ATF4
GRP75
PCK2
VDAC1
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
14 04 2020
14 04 2020
Historique:
received:
03
06
2019
revised:
21
12
2019
accepted:
21
03
2020
entrez:
16
4
2020
pubmed:
16
4
2020
medline:
28
4
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32294449
pii: S2211-1247(20)30396-X
doi: 10.1016/j.celrep.2020.03.070
pii:
doi:
Substances chimiques
Cell Cycle Proteins
0
Cytoskeletal Proteins
0
HSP70 Heat-Shock Proteins
0
HSPA9 protein, human
0
MCPH1 protein, human
0
Mitochondrial Proteins
0
Nerve Tissue Proteins
0
VDAC1 protein, human
0
Voltage-Dependent Anion Channel 1
EC 1.6.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107506Informations de copyright
Copyright © 2020 Institut National de la Sante et de la Recherche Médicale. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.