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.
Keywords:
Charcot-Marie-Tooth type 2A; Drp1; Mfn1 and Mfn2; Opa1; developmental biology; drosophila melanogaster; endoplasmic reticulum; lipid droplets; mitochondria transport; neuroscience; stem cells.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Genetically Modified
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Axons / metabolism
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Cholesterol / metabolism
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism
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Drosophila Proteins / deficiency
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Drosophila Proteins / genetics*
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Drosophila Proteins / metabolism
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Drosophila melanogaster / genetics*
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Drosophila melanogaster / growth & development
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Drosophila melanogaster / metabolism
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Ecdysone / biosynthesis*
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Endoplasmic Reticulum / metabolism
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Endoplasmic Reticulum / ultrastructure
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GTP Phosphohydrolases / genetics
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GTP Phosphohydrolases / metabolism
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / metabolism
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Gene Expression Regulation, Developmental
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Genetic Complementation Test
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Humans
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Larva / genetics
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Larva / growth & development
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Larva / metabolism
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Lipid Droplets / metabolism
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Longevity / genetics
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Membrane Proteins / deficiency
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Membrane Proteins / genetics*
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Mitochondria / genetics*
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Mitochondria / metabolism
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Mitochondrial Dynamics / genetics*
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Mitochondrial Membrane Transport Proteins / genetics
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Mitochondrial Membrane Transport Proteins / metabolism
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Mitochondrial Proteins / genetics
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Mitochondrial Proteins / metabolism
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Neuromuscular Junction / genetics
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Neuromuscular Junction / metabolism
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Synapses / genetics
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Synapses / metabolism*
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Synaptic Transmission
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rho GTP-Binding Proteins / genetics
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rho GTP-Binding Proteins / metabolism
Substances
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Cytoskeletal Proteins
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Drosophila Proteins
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Marf protein, Drosophila
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Membrane Proteins
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Mitochondrial Membrane Transport Proteins
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Mitochondrial Proteins
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Ecdysone
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Cholesterol
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DRP1 protein, Drosophila
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GTP Phosphohydrolases
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GTP-Binding Proteins
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MFN2 protein, human
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Miro protein, Drosophila
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Mfn1 protein, human
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rho GTP-Binding Proteins