1. Cell Biology
  2. Neuroscience
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Glycolytic reliance promotes anabolism in photoreceptors

  1. Yashodhan Chinchore
  2. Tedi Begaj
  3. David Wu
  4. Eugene Drokhlyansky
  5. Constance L Cepko  Is a corresponding author
  1. Harvard Medical School, United States
Research Article
  • Cited 45
  • Views 2,225
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Cite this article as: eLife 2017;6:e25946 doi: 10.7554/eLife.25946

Abstract

Vertebrate photoreceptors are among the most metabolically active cells, exhibiting a high rate of ATP consumption. This is coupled with a high anabolic demand, necessitated by the diurnal turnover of a specialized membrane-rich organelle, the outer segment, which is the primary site of phototransduction. How photoreceptors balance their catabolic and anabolic demands is poorly understood. Here, we show that rod photoreceptors in mice rely on glycolysis for their outer segment biogenesis. Genetic perturbations targeting allostery or key regulatory nodes in the glycolytic pathway impacted the size of the outer segments. Fibroblast growth factor signaling was found to regulate glycolysis, with antagonism of this pathway resulting in anabolic deficits. These data demonstrate the cell autonomous role of the glycolytic pathway in outer segment maintenance and provide evidence that aerobic glycolysis is part of a metabolic program that supports the biosynthetic needs of a normal neuronal cell type.

Article and author information

Author details

  1. Yashodhan Chinchore

    Department of Genetics, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Tedi Begaj

    Department of Genetics, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. David Wu

    Department of Genetics, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Eugene Drokhlyansky

    Department of Genetics, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Constance L Cepko

    Department of Genetics, Harvard Medical School, Boston, United States
    For correspondence
    cepko@genetics.med.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9945-6387

Funding

National Institutes of Health (R01 EY023291)

  • Yashodhan Chinchore
  • Tedi Begaj
  • David Wu
  • Eugene Drokhlyansky
  • Constance L Cepko

Howard Hughes Medical Institute

  • Constance L Cepko

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animal care and use adhered to the Harvard Medical School's IACUC guidelines. Animals were handled in accordance with the protocol# 0428 and 04537.

Reviewing Editor

  1. Jeremy Nathans, Johns Hopkins University School of Medicine, United States

Publication history

  1. Received: February 17, 2017
  2. Accepted: June 1, 2017
  3. Accepted Manuscript published: June 9, 2017 (version 1)
  4. Version of Record published: July 6, 2017 (version 2)

Copyright

© 2017, Chinchore et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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