Mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone production

  1. Hector Sandoval
  2. Chi-Kuang Yao
  3. Kuchuan Chen
  4. Manish Jaiswal
  5. Taraka Donti
  6. Yong Qi Lin
  7. Vafa Bayat
  8. Bo Xiong
  9. Ke Zhang
  10. Gabriela David
  11. Wu-Lin Charng
  12. Yamamoto Shinya
  13. Lita Duraine
  14. Brett H Graham
  15. Hugo J Bellen  Is a corresponding author
  1. Baylor College of Medicine, United States
  2. Academia Sinica, Taiwan
  3. Howard Hughes Medical Institute, Baylor College Of Medicine, United States
  4. Stanford Hospital and Clinics, United States
  5. University of Washington, United States
  6. John Hopkins University, United States
  7. Howard Hughes Medical Institute, Baylor College of Medicine, United States

Abstract

Mitochondrial fusion and fission affect the distribution and quality control of mitochondria. We show that Marf (Mitochondrial associated regulatory factor), is required for mitochondrial fusion and transport in long axons. Moreover, loss of Marf leads to a severe depletion of mitochondria in neuromuscular junctions (NMJs). Marf mutants also fail to maintain proper synaptic transmission at NMJs upon repetitive stimulation, similar to Drp1 fission mutants. However, unlike Drp1, loss of Marf leads to NMJ morphology defects and extended larval lifespan. Marf is required to form contacts between the endoplasmic reticulum and/or lipid droplets (LDs) and for proper storage of cholesterol and ecdysone synthesis in Ring Glands. Interestingly, human Mitofusin-2 rescues the loss of LD but both Mitofusin-1 and Mitofusin-2 are required for steroid-hormone synthesis. Our data show that Marf and Mitofusins share an evolutionarily conserved role in mitochondrial transport, cholesterol ester storage and steroid-hormone synthesis.

Article and author information

Author details

  1. Hector Sandoval

    Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Chi-Kuang Yao

    Academia Sinica, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  3. Kuchuan Chen

    Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Manish Jaiswal

    Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Taraka Donti

    Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Yong Qi Lin

    Howard Hughes Medical Institute, Baylor College Of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Vafa Bayat

    Stanford Hospital and Clinics, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Bo Xiong

    University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Ke Zhang

    John Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Gabriela David

    Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Wu-Lin Charng

    Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Yamamoto Shinya

    Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Lita Duraine

    Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Brett H Graham

    Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Hugo J Bellen

    Baylor College of Medicine, Houston, United States
    For correspondence
    hbellen@bcm.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Richard J Youle, National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States

Version history

  1. Received: June 2, 2014
  2. Accepted: October 13, 2014
  3. Accepted Manuscript published: October 14, 2014 (version 1)
  4. Version of Record published: November 3, 2014 (version 2)

Copyright

© 2014, Sandoval 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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  1. Hector Sandoval
  2. Chi-Kuang Yao
  3. Kuchuan Chen
  4. Manish Jaiswal
  5. Taraka Donti
  6. Yong Qi Lin
  7. Vafa Bayat
  8. Bo Xiong
  9. Ke Zhang
  10. Gabriela David
  11. Wu-Lin Charng
  12. Yamamoto Shinya
  13. Lita Duraine
  14. Brett H Graham
  15. Hugo J Bellen
(2014)
Mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone production
eLife 3:e03558.
https://doi.org/10.7554/eLife.03558

Share this article

https://doi.org/10.7554/eLife.03558

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