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Neuron. 2017 Feb 8;93(3):560-573.e6. doi: 10.1016/j.neuron.2016.12.017. Epub 2017 Jan 19.

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

Author information

1
Institute of Biochemistry, Emil Fischer Center, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany. Electronic address: ruth.beckervordersandforth@fau.de.
2
Institute of Biochemistry, Emil Fischer Center, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany; Institute of Developmental Genetics, Helmholtz Center Munich, German Research Center for Environmental Health, 85764 Munich-Neuherberg, Germany.
3
Institute of Biochemistry, Emil Fischer Center, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
4
Department of Fundamental Neuroscience, University of Lausanne, 1005 Lausanne, Switzerland.
5
Institute for Cell Engineering, Department of Neurology, The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
6
Brain Research Institute, Faculty of Medicine and Science, University of Zurich, 8057 Zurich, Switzerland.
7
Laboratory of Neuronal Plasticity, Leloir Institute (IIBBA, CONICET), C1405BWE Buenos Aires, Argentina.
8
Molecular and Clinical Pharmacy, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
9
Institute of Developmental Genetics, Helmholtz Center Munich, German Research Center for Environmental Health, 85764 Munich-Neuherberg, Germany.
10
Hans Berger Department of Neurology, Jena University Hospital, 07747 Jena, Germany.
11
Institute of Developmental Genetics, Helmholtz Center Munich, German Research Center for Environmental Health, 85764 Munich-Neuherberg, Germany; F. Hoffmann-La Roche Ltd, CNS Discovery; Pharma Research and Early Development, 4070 Basel, Switzerland.
12
Institute of Biochemistry, Emil Fischer Center, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany. Electronic address: chi.lie@fau.de.

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.

KEYWORDS:

adult neurogenesis; aging; metabolism; mitochondria; stem cells

PMID:
28111078
PMCID:
PMC5300896
DOI:
10.1016/j.neuron.2016.12.017
[Indexed for MEDLINE]
Free PMC Article

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