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

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. SchinderGuo li Ming, Nicolas Toni, Sebastian Jessberger, Hongjun Song, D. Chichung Lie

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)560-573.e6
JournalNeuron
Volume93
Issue number3
DOIs
StatePublished - Feb 8 2017

Keywords

  • adult neurogenesis
  • aging
  • metabolism
  • mitochondria
  • stem cells

ASJC Scopus subject areas

  • Neuroscience(all)

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    Beckervordersandforth, R., Ebert, B., Schäffner, I., Moss, J., Fiebig, C., Shin, J., Moore, D. L., Ghosh, L., Trinchero, M. F., Stockburger, C., Friedland, K., Steib, K., von Wittgenstein, J., Keiner, S., Redecker, C., Hölter, S. M., Xiang, W., Wurst, W., Jagasia, R., ... Lie, D. C. (2017). Role of Mitochondrial Metabolism in the Control of Early Lineage Progression and Aging Phenotypes in Adult Hippocampal Neurogenesis. Neuron, 93(3), 560-573.e6. https://doi.org/10.1016/j.neuron.2016.12.017