title: Role of Mitochondrial Metabolism in the Control of Early Lineage Progression and Aging Phenotypes in Adult Hippocampal Neurogenesis.
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.
authors.affiliation: Institute of Biochemistry, Emil Fischer Center, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany. Electronic address: ruth.beckervordersandforth@fau.de.
authors.forename: Ruth
authors.initials: R
authors.lastname: Beckervordersandforth
authors.affiliation: 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.
authors.forename: Birgit
authors.initials: B
authors.lastname: Ebert
authors.affiliation: Institute of Biochemistry, Emil Fischer Center, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Schäffner
authors.affiliation: Department of Fundamental Neuroscience, University of Lausanne, 1005 Lausanne, Switzerland.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Moss
authors.affiliation: Institute of Biochemistry, Emil Fischer Center, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Fiebig
authors.affiliation: Institute for Cell Engineering, Department of Neurology, The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Shin
authors.affiliation: Brain Research Institute, Faculty of Medicine and Science, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Darcie L
authors.initials: DL
authors.lastname: Moore
authors.affiliation: Brain Research Institute, Faculty of Medicine and Science, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Laboni
authors.initials: L
authors.lastname: Ghosh
authors.affiliation: Laboratory of Neuronal Plasticity, Leloir Institute (IIBBA, CONICET), C1405BWE Buenos Aires, Argentina.
authors.forename: Mariela F
authors.initials: MF
authors.lastname: Trinchero
authors.affiliation: Molecular and Clinical Pharmacy, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Stockburger
authors.affiliation: Molecular and Clinical Pharmacy, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Friedland
authors.affiliation: Institute of Developmental Genetics, Helmholtz Center Munich, German Research Center for Environmental Health, 85764 Munich-Neuherberg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Steib
authors.affiliation: Institute of Biochemistry, Emil Fischer Center, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: von Wittgenstein
authors.affiliation: Hans Berger Department of Neurology, Jena University Hospital, 07747 Jena, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Keiner
authors.affiliation: Hans Berger Department of Neurology, Jena University Hospital, 07747 Jena, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Redecker
authors.affiliation: Institute of Developmental Genetics, Helmholtz Center Munich, German Research Center for Environmental Health, 85764 Munich-Neuherberg, Germany.
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Hölter
authors.affiliation: Institute of Biochemistry, Emil Fischer Center, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiang
authors.affiliation: Institute of Developmental Genetics, Helmholtz Center Munich, German Research Center for Environmental Health, 85764 Munich-Neuherberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.affiliation: 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.
authors.forename: Ravi
authors.initials: R
authors.lastname: Jagasia
authors.affiliation: Laboratory of Neuronal Plasticity, Leloir Institute (IIBBA, CONICET), C1405BWE Buenos Aires, Argentina.
authors.forename: Alejandro F
authors.initials: AF
authors.lastname: Schinder
authors.affiliation: Institute for Cell Engineering, Department of Neurology, The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Guo-Li
authors.initials: GL
authors.lastname: Ming
authors.affiliation: Department of Fundamental Neuroscience, University of Lausanne, 1005 Lausanne, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Toni
authors.affiliation: Brain Research Institute, Faculty of Medicine and Science, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Jessberger
authors.affiliation: Institute for Cell Engineering, Department of Neurology, The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Song
authors.affiliation: Institute of Biochemistry, Emil Fischer Center, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany. Electronic address: chi.lie@fau.de.
authors.forename: D Chichung
authors.initials: DC
authors.lastname: Lie
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D006609:High Mobility Group Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D058953:Neural Stem Cells; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010085:Oxidative Phosphorylation
chemical_list: D004268:DNA-Binding Proteins; D045222:Electron Transport Chain Complex Proteins; D006609:High Mobility Group Proteins; C081930:Tfam protein, mouse
keywords: adult neurogenesis; aging; metabolism; mitochondria; stem cells