The autophagy regulators Ambra1 and Beclin 1 are required for adult neurogenesis in the brain subventricular zone

M. Yazdankhah, S. Farioli-Vecchioli, A. B. Tonchev, A. Stoykova, F. Cecconi

Research output: Contribution to journalArticle

Abstract

Autophagy is a conserved proteolytic mechanism required for maintaining cellular homeostasis. The role of this process in vertebrate neural development is related to metabolic needs and stress responses, even though the importance of its progression has been observed in a number of circumstances, both in embryonic and in postnatal differentiating tissues. Here we show that the proautophagic proteins Ambra1 and Beclin 1, involved in the initial steps of autophagosome formation, are highly expressed in the adult subventricular zone (SVZ), whereas their downregulation in adult neural stem cells in vitro leads to a decrease in cell proliferation, an increase in basal apoptosis and an augmented sensitivity to DNA-damage-induced death. Further, Beclin 1 heterozygosis in vivo results in a significant reduction of proliferating cells and immature neurons in the SVZ, accompanied by a marked increase in apoptotic cell death. In sum, we propose that Ambra1- and Beclin 1-mediated autophagy plays a crucial role in adult neurogenesis, by controlling the survival of neural precursor cells.

Original languageEnglish
Article numbere1403
JournalCell Death and Disease
Volume5
Issue number9
DOIs
Publication statusPublished - Jan 1 2014

Fingerprint

Lateral Ventricles
Neurogenesis
Autophagy
Brain
Physiological Stress
Adult Stem Cells
Neural Stem Cells
DNA Damage
Vertebrates
Homeostasis
Cell Death
Down-Regulation
Cell Proliferation
Apoptosis
Neurons
Beclin-1

ASJC Scopus subject areas

  • Cell Biology
  • Immunology
  • Cancer Research
  • Cellular and Molecular Neuroscience

Cite this

The autophagy regulators Ambra1 and Beclin 1 are required for adult neurogenesis in the brain subventricular zone. / Yazdankhah, M.; Farioli-Vecchioli, S.; Tonchev, A. B.; Stoykova, A.; Cecconi, F.

In: Cell Death and Disease, Vol. 5, No. 9, e1403, 01.01.2014.

Research output: Contribution to journalArticle

Yazdankhah, M. ; Farioli-Vecchioli, S. ; Tonchev, A. B. ; Stoykova, A. ; Cecconi, F. / The autophagy regulators Ambra1 and Beclin 1 are required for adult neurogenesis in the brain subventricular zone. In: Cell Death and Disease. 2014 ; Vol. 5, No. 9.
@article{9ae7163275b4473f828cc64253611b1c,
title = "The autophagy regulators Ambra1 and Beclin 1 are required for adult neurogenesis in the brain subventricular zone",
abstract = "Autophagy is a conserved proteolytic mechanism required for maintaining cellular homeostasis. The role of this process in vertebrate neural development is related to metabolic needs and stress responses, even though the importance of its progression has been observed in a number of circumstances, both in embryonic and in postnatal differentiating tissues. Here we show that the proautophagic proteins Ambra1 and Beclin 1, involved in the initial steps of autophagosome formation, are highly expressed in the adult subventricular zone (SVZ), whereas their downregulation in adult neural stem cells in vitro leads to a decrease in cell proliferation, an increase in basal apoptosis and an augmented sensitivity to DNA-damage-induced death. Further, Beclin 1 heterozygosis in vivo results in a significant reduction of proliferating cells and immature neurons in the SVZ, accompanied by a marked increase in apoptotic cell death. In sum, we propose that Ambra1- and Beclin 1-mediated autophagy plays a crucial role in adult neurogenesis, by controlling the survival of neural precursor cells.",
author = "M. Yazdankhah and S. Farioli-Vecchioli and Tonchev, {A. B.} and A. Stoykova and F. Cecconi",
year = "2014",
month = "1",
day = "1",
doi = "10.1038/cddis.2014.358",
language = "English",
volume = "5",
journal = "Cell Death and Disease",
issn = "2041-4889",
publisher = "Nature Publishing Group",
number = "9",

}

TY - JOUR

T1 - The autophagy regulators Ambra1 and Beclin 1 are required for adult neurogenesis in the brain subventricular zone

AU - Yazdankhah, M.

AU - Farioli-Vecchioli, S.

AU - Tonchev, A. B.

AU - Stoykova, A.

AU - Cecconi, F.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Autophagy is a conserved proteolytic mechanism required for maintaining cellular homeostasis. The role of this process in vertebrate neural development is related to metabolic needs and stress responses, even though the importance of its progression has been observed in a number of circumstances, both in embryonic and in postnatal differentiating tissues. Here we show that the proautophagic proteins Ambra1 and Beclin 1, involved in the initial steps of autophagosome formation, are highly expressed in the adult subventricular zone (SVZ), whereas their downregulation in adult neural stem cells in vitro leads to a decrease in cell proliferation, an increase in basal apoptosis and an augmented sensitivity to DNA-damage-induced death. Further, Beclin 1 heterozygosis in vivo results in a significant reduction of proliferating cells and immature neurons in the SVZ, accompanied by a marked increase in apoptotic cell death. In sum, we propose that Ambra1- and Beclin 1-mediated autophagy plays a crucial role in adult neurogenesis, by controlling the survival of neural precursor cells.

AB - Autophagy is a conserved proteolytic mechanism required for maintaining cellular homeostasis. The role of this process in vertebrate neural development is related to metabolic needs and stress responses, even though the importance of its progression has been observed in a number of circumstances, both in embryonic and in postnatal differentiating tissues. Here we show that the proautophagic proteins Ambra1 and Beclin 1, involved in the initial steps of autophagosome formation, are highly expressed in the adult subventricular zone (SVZ), whereas their downregulation in adult neural stem cells in vitro leads to a decrease in cell proliferation, an increase in basal apoptosis and an augmented sensitivity to DNA-damage-induced death. Further, Beclin 1 heterozygosis in vivo results in a significant reduction of proliferating cells and immature neurons in the SVZ, accompanied by a marked increase in apoptotic cell death. In sum, we propose that Ambra1- and Beclin 1-mediated autophagy plays a crucial role in adult neurogenesis, by controlling the survival of neural precursor cells.

UR - http://www.scopus.com/inward/record.url?scp=84921792662&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84921792662&partnerID=8YFLogxK

U2 - 10.1038/cddis.2014.358

DO - 10.1038/cddis.2014.358

M3 - Article

C2 - 25188513

AN - SCOPUS:84921792662

VL - 5

JO - Cell Death and Disease

JF - Cell Death and Disease

SN - 2041-4889

IS - 9

M1 - e1403

ER -