Mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone production
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 neurom...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2014-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/03558 |
| _version_ | 1811200084766883840 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Hector Sandoval |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T01:58:54Z |
| format | Article |
| id | doaj.art-2d6f9a4e1a134a21898c519ca66c09b9 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:58:54Z |
| publishDate | 2014-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-2d6f9a4e1a134a21898c519ca66c09b92022-12-22T03:52:44ZengeLife Sciences Publications LtdeLife2050-084X2014-10-01310.7554/eLife.03558Mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone productionHector Sandoval0Chi-Kuang Yao1Kuchuan Chen2Manish Jaiswal3Taraka Donti4Yong Qi Lin5Vafa Bayat6Bo Xiong7Ke Zhang8Gabriela David9Wu-Lin Charng10Shinya Yamamoto11Lita Duraine12Brett H Graham13Hugo J Bellen14Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United StatesDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, United StatesProgram in Developmental Biology, Baylor College of Medicine, Houston, United StatesDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United StatesDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, United StatesHoward Hughes Medical Institute, Baylor College of Medicine, Houston, United StatesProgram in Developmental Biology, Baylor College of Medicine, Houston, United States; Medical Scientist Training Program, Baylor College of Medicine, Houston, United StatesProgram in Developmental Biology, Baylor College of Medicine, Houston, United StatesProgram in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, United StatesProgram in Developmental Biology, Baylor College of Medicine, Houston, United StatesDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States; Program in Developmental Biology, Baylor College of Medicine, Houston, United StatesDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States; Program in Developmental Biology, Baylor College of Medicine, Houston, United States; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United StatesHoward Hughes Medical Institute, Baylor College of Medicine, Houston, United StatesDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States; Program in Developmental Biology, Baylor College of Medicine, Houston, United StatesDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States; Program in Developmental Biology, Baylor College of Medicine, Houston, United States; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States; Department of Neuroscience, Baylor College of Medicine, Houston, United StatesMitochondrial 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.https://elifesciences.org/articles/03558mitochondria transportCharcot-Marie-Tooth type 2AMfn1Drp1Opa1lipid droplet |
| spellingShingle | 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 Mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone production eLife mitochondria transport Charcot-Marie-Tooth type 2A Mfn1 Drp1 Opa1 lipid droplet |
| title | Mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone production |
| title_full | Mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone production |
| title_fullStr | Mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone production |
| title_full_unstemmed | Mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone production |
| title_short | Mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone production |
| title_sort | mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone production |
| topic | mitochondria transport Charcot-Marie-Tooth type 2A Mfn1 Drp1 Opa1 lipid droplet |
| url | https://elifesciences.org/articles/03558 |
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