title: Mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone production.
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.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.
authors.forename: Hector
authors.initials: H
authors.lastname: Sandoval
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.
authors.forename: Chi-Kuang
authors.initials: CK
authors.lastname: Yao
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, United States.
authors.forename: Kuchuan
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.
authors.forename: Manish
authors.initials: M
authors.lastname: Jaiswal
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.
authors.forename: Taraka
authors.initials: T
authors.lastname: Donti
authors.affiliation: Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States.
authors.forename: Yong Qi
authors.initials: YQ
authors.lastname: Lin
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, United States.
authors.forename: Vafa
authors.initials: V
authors.lastname: Bayat
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, United States.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiong
authors.affiliation: Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, United States.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, United States.
authors.forename: Gabriela
authors.initials: G
authors.lastname: David
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.
authors.forename: Wu-Lin
authors.initials: WL
authors.lastname: Charng
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States.
authors.forename: Lita
authors.initials: L
authors.lastname: Duraine
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.
authors.forename: Brett H
authors.initials: BH
authors.lastname: Graham
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.
authors.forename: Hugo J
authors.initials: HJ
authors.lastname: Bellen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D004440:Ecdysone / Q000096:biosynthesis*; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005816:Genetic Complementation Test; D006801:Humans; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D066292:Lipid Droplets / Q000378:metabolism; D008136:Longevity / Q000235:genetics; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000235:genetics*; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; C527117:Marf protein, Drosophila; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D004440:Ecdysone; D002784:Cholesterol; C504426:DRP1 protein, Drosophila; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C470018:MFN2 protein, human; C504427:Miro protein, Drosophila; C470017:Mfn1 protein, human; D020741:rho GTP-Binding Proteins
keywords: Charcot-Marie-Tooth type 2A; Drp1; Mfn1 and Mfn2; Opa1; developmental biology; drosophila melanogaster; endoplasmic reticulum; lipid droplets; mitochondria transport; neuroscience; stem cells