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

Hector Sandoval, Chi Kuang Yao, Kuchuan Chen, Manish Jaiswal, Taraka Donti, Yong Qi Lin, Vafa Bayat, Bo Xiong, Ke Zhang, Gabriela David, Wu Lin Charng, Shinya Yamamoto, Lita Duraine, Brett H. Graham, Hugo J. Bellen

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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 steroidhormone synthesis. Our data show that Marf and Mitofusins share an evolutionarily conserved role in mitochondrial transport, cholesterol ester storage and steroid-hormone synthesis.

Original languageEnglish (US)
Article numbere03558
Pages (from-to)1-23
Number of pages23
JournaleLife
Volume3
Issue numberOctober2014
DOIs
StatePublished - Oct 1 2014

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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