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

doi:10.7554/eLife.03558

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 Institute

Research output: Contribution to journal › Article

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 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.

Original language	English (US)
Journal	eLife
Volume	3
DOIs	https://doi.org/10.7554/eLife.03558
State	Published - Oct 14 2014

Keywords

Animals
Animals, Genetically Modified
Axons
Cholesterol
Cytoskeletal Proteins
Drosophila Proteins
Drosophila melanogaster
Ecdysone
Endoplasmic Reticulum
GTP Phosphohydrolases
GTP-Binding Proteins
Gene Expression Regulation, Developmental
Genetic Complementation Test
Humans
Larva
Lipid Droplets
Longevity
Membrane Proteins
Mitochondria
Mitochondrial Dynamics
Mitochondrial Membrane Transport Proteins
Mitochondrial Proteins
Neuromuscular Junction
Synapses
Synaptic Transmission
rho GTP-Binding Proteins
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

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Mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone production. / Sandoval, Hector; Yao, Chi-Kuang; Chen, Kuchuan; Jaiswal, Manish; Donti, Taraka; Lin, Yong Qi; Bayat, Vafa; Xiong, Bo; Zhang, Ke; David, Gabriela; Charng, Wu-Lin; Yamamoto, Shinya; Duraine, Lita; Graham, Brett H; Bellen, Hugo J.

In: eLife, Vol. 3, 14.10.2014.

Research output: Contribution to journal › Article

Sandoval, Hector ; Yao, Chi-Kuang ; Chen, Kuchuan ; Jaiswal, Manish ; Donti, Taraka ; Lin, Yong Qi ; Bayat, Vafa ; Xiong, Bo ; Zhang, Ke ; David, Gabriela ; Charng, Wu-Lin ; Yamamoto, Shinya ; Duraine, Lita ; Graham, Brett H ; Bellen, Hugo J. / Mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone production. In: eLife. 2014 ; Vol. 3.

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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.",

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

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AU - Yao, Chi-Kuang

AU - Chen, Kuchuan

AU - Jaiswal, Manish

AU - Donti, Taraka

AU - Lin, Yong Qi

AU - Bayat, Vafa

AU - Xiong, Bo

AU - Zhang, Ke

AU - David, Gabriela

AU - Charng, Wu-Lin

AU - Yamamoto, Shinya

AU - Duraine, Lita

AU - Graham, Brett H

AU - Bellen, Hugo J

PY - 2014/10/14

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N2 - 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.

AB - 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.

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KW - Cholesterol

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KW - Endoplasmic Reticulum

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KW - Genetic Complementation Test

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KW - rho GTP-Binding Proteins

KW - Journal Article

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KW - Research Support, Non-U.S. Gov't

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DO - 10.7554/eLife.03558

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SN - 2050-084X

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