Role of Mitochondrial Metabolism in the Control of Early Lineage Progression and Aging Phenotypes in Adult Hippocampal Neurogenesis

Autoren

Ruth Beckervordersandforth
Birgit Ebert
Iris Schäffner
Jonathan Moss
Christian Fiebig
Jaehoon Shin
Darcie L Moore
Laboni Ghosh
Mariela F Trinchero
Carola Stockburger
Kristina Friedland
Kathrin Steib
Julia von Wittgenstein
Silke Keiner
Christoph Redecker
Sabine M Hölter
Wei Xiang
Wolfgang Wurst
Ravi Jagasia
Alejandro F Schinder
Guo-li Ming
Nicolas Toni
Sebastian Jessberger
Hongjun Song
D Chichung Lie

DOI

10.1016/j.neuron.2016.12.017

ISSN

0896-6273

Ausgabe der Veröffentlichung

3

Zeitschrift

Neuron

Sprache

en

Paginierung

560 - 573.e6

Datum der Veröffentlichung

2017

Status

Published

Herausgeber

Elsevier BV

Herausgeber URL

http://dx.doi.org/10.1016/j.neuron.2016.12.017

Datum der Datenerfassung

2022

Titel

Role of Mitochondrial Metabolism in the Control of Early Lineage Progression and Aging Phenotypes in Adult Hippocampal Neurogenesis

Ausgabe der Zeitschrift

93

Datenquelle: Crossref

Abstract

Precise regulation of cellular metabolism is hypothesized to constitute a vital component of the developmental sequence underlying the life-long generation of hippocampal neurons from quiescent neural stem cells (NSCs). The identity of stage-specific metabolic programs and their impact on adult neurogenesis are largely unknown. We show that the adult hippocampal neurogenic lineage is critically dependent on the mitochondrial electron transport chain and oxidative phosphorylation machinery at the stage of the fast proliferating intermediate progenitor cell. Perturbation of mitochondrial complex function by ablation of the mitochondrial transcription factor A (Tfam) reproduces multiple hallmarks of aging in hippocampal neurogenesis, whereas pharmacological enhancement of mitochondrial function ameliorates age-associated neurogenesis defects. Together with the finding of age-associated alterations in mitochondrial function and morphology in NSCs, these data link mitochondrial complex function to efficient lineage progression of adult NSCs and identify mitochondrial function as a potential target to ameliorate neurogenesis-defects in the aging hippocampus.

Addresses

Institute of Biochemistry, Emil Fischer Center, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany. Electronic address: ruth.beckervordersandforth@fau.de.

Autoren

Ruth Beckervordersandforth
Birgit Ebert
Iris Schäffner
Jonathan Moss
Christian Fiebig
Jaehoon Shin
Darcie L Moore
Laboni Ghosh
Mariela F Trinchero
Carola Stockburger
Kristina Friedland
Kathrin Steib
Julia von Wittgenstein
Silke Keiner
Christoph Redecker
Sabine M Hölter
Wei Xiang
Wolfgang Wurst
Ravi Jagasia
Alejandro F Schinder
Guo-Li Ming
Nicolas Toni
Sebastian Jessberger
Hongjun Song
D Chichung Lie

DOI

10.1016/j.neuron.2016.12.017

eISSN

1097-4199

Externe Identifier

PubMed Identifier: 28111078
PubMed Central ID: PMC5300896

Funding acknowledgements

Deutsche Forschungsgemeinschaft: DFG GRK2162/1
NIH: P01 NS097206
NINDS NIH HHS: R35 NS097370
Helmholtz Alliance for Mental Health in an Ageing Society:
NIH: R35NS097370
German Research Foundation: INST 410/45-1 FUGG
Swiss National Science Foundation: PPOOA-119026/1
German Research Foundation: 9-1
University Hospital Erlangen: E12
NIMH NIH HHS: R01 MH105128
Bavarian Research Network “ForIPS,”:
Schering foundation:
University Hospital Erlangen: E16
University Hospital Erlangen: E21
NIH: R01MH105128
NINDS NIH HHS: P01 NS097206
NIH: R37NS047344
Swiss National Science Foundation: SNSF 31003A-156943
German Research Foundation: BE 5136/1-1
University Hospital Erlangen: E11
German Research Foundation: LI 858/6-3
NINDS NIH HHS: R37 NS047344

Open access

false

ISSN

0896-6273

Ausgabe der Veröffentlichung

3

Zeitschrift

Neuron

Schlüsselwörter

Hippocampus
Neurons
Cells, Cultured
Mitochondria
Animals
Mice, Transgenic
Mice, Knockout
Mice
Electron Transport Chain Complex Proteins
DNA-Binding Proteins
High Mobility Group Proteins
Cell Proliferation
Oxidative Phosphorylation
Cell Lineage
Aging
Adult Stem Cells
Neurogenesis
Neural Stem Cells

Sprache

eng

Medium

Print-Electronic

Online publication date

2017

Paginierung

560 - 573.e6

Datum der Veröffentlichung

2017

Status

Published

Datum der Datenerfassung

2017

Titel

Role of Mitochondrial Metabolism in the Control of Early Lineage Progression and Aging Phenotypes in Adult Hippocampal Neurogenesis.

Sub types

Video-Audio Media
research-article
Journal Article

Ausgabe der Zeitschrift

93

Files

http://www.cell.com/article/S089662731630959X/pdf https://europepmc.org/articles/PMC5300896?pdf=render

Datenquelle: Europe PubMed Central

Abstract

Precise regulation of cellular metabolism is hypothesized to constitute a vital component of the developmental sequence underlying the life-long generation of hippocampal neurons from quiescent neural stem cells (NSCs). The identity of stage-specific metabolic programs and their impact on adult neurogenesis are largely unknown. We show that the adult hippocampal neurogenic lineage is critically dependent on the mitochondrial electron transport chain and oxidative phosphorylation machinery at the stage of the fast proliferating intermediate progenitor cell. Perturbation of mitochondrial complex function by ablation of the mitochondrial transcription factor A (Tfam) reproduces multiple hallmarks of aging in hippocampal neurogenesis, whereas pharmacological enhancement of mitochondrial function ameliorates age-associated neurogenesis defects. Together with the finding of age-associated alterations in mitochondrial function and morphology in NSCs, these data link mitochondrial complex function to efficient lineage progression of adult NSCs and identify mitochondrial function as a potential target to ameliorate neurogenesis-defects in the aging hippocampus.

Date of acceptance

2016

Autoren

Ruth Beckervordersandforth
Birgit Ebert
Iris Schäffner
Jonathan Moss
Christian Fiebig
Jaehoon Shin
Darcie L Moore
Laboni Ghosh
Mariela F Trinchero
Carola Stockburger
Kristina Friedland
Kathrin Steib
Julia von Wittgenstein
Silke Keiner
Christoph Redecker
Sabine M Hölter
Wei Xiang
Wolfgang Wurst
Ravi Jagasia
Alejandro F Schinder
Guo-Li Ming
Nicolas Toni
Sebastian Jessberger
Hongjun Song
D Chichung Lie

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/28111078

DOI

10.1016/j.neuron.2016.12.017

eISSN

1097-4199

Externe Identifier

NIH Manuscript Submission ID: NIHMS837585
PubMed Central ID: PMC5300896

Funding acknowledgements

NINDS NIH HHS: P01 NS097206
NIMH NIH HHS: R01 MH105128
NINDS NIH HHS: R35 NS097370
NINDS NIH HHS: R37 NS047344

Ausgabe der Veröffentlichung

3

Zeitschrift

Neuron

Schlüsselwörter

adult neurogenesis
aging
metabolism
mitochondria
stem cells
Adult Stem Cells
Aging
Animals
Cell Lineage
Cell Proliferation
Cells, Cultured
DNA-Binding Proteins
Electron Transport Chain Complex Proteins
High Mobility Group Proteins
Hippocampus
Mice
Mice, Knockout
Mice, Transgenic
Mitochondria
Neural Stem Cells
Neurogenesis
Neurons
Oxidative Phosphorylation

Sprache

eng

Country

United States

Paginierung

560 - 573.e6

PII

S0896-6273(16)30959-X

Datum der Veröffentlichung

2017

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2017

Titel

Role of Mitochondrial Metabolism in the Control of Early Lineage Progression and Aging Phenotypes in Adult Hippocampal Neurogenesis.

Sub types

Journal Article
Video-Audio Media

Ausgabe der Zeitschrift

93

Datenquelle: PubMed

Role of Mitochondrial Metabolism in the Control of Early Lineage Progression and Aging Phenotypes in Adult Hippocampal Neurogenesis

Files

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