Mitofusin 2 Regulates Axonal Transport of Calpastatin to Prevent Neuromuscular Synaptic Elimination in Skeletal Muscles
Copyright © 2018 Elsevier Inc. All rights reserved..
Skeletal muscles undergo atrophy in response to diseases and aging. Here we report that mitofusin 2 (Mfn2) acts as a dominant suppressor of neuromuscular synaptic loss to preserve skeletal muscles. Mfn2 is reduced in spinal cords of transgenic SOD1G93A and aged mice. Through preserving neuromuscular synapses, increasing neuronal Mfn2 prevents skeletal muscle wasting in both SOD1G93A and aged mice, whereas deletion of neuronal Mfn2 produces neuromuscular synaptic dysfunction and skeletal muscle atrophy. Neuromuscular synaptic loss after sciatic nerve transection can also be alleviated by Mfn2. Mfn2 coexists with calpastatin largely in mitochondria-associated membranes (MAMs) to regulate its axonal transport. Genetic inactivation of calpastatin abolishes Mfn2-mediated protection of neuromuscular synapses. Our results suggest that, as a potential key component of a novel and heretofore unrecognized mechanism of cytoplasmic protein transport, Mfn2 may play a general role in preserving neuromuscular synapses and serve as a common therapeutic target for skeletal muscle atrophy.
| Errataetall: |
CommentIn: Cell Metab. 2018 Oct 2;28(4):536-538. - PMID 30282045 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:28 |
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| Enthalten in: |
Cell metabolism - 28(2018), 3 vom: 04. Sept., Seite 400-414.e8 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Luwen [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.10.2019 Date Revised 09.07.2021 published: Print-Electronic CommentIn: Cell Metab. 2018 Oct 2;28(4):536-538. - PMID 30282045 Citation Status MEDLINE |
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| doi: |
10.1016/j.cmet.2018.06.011 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM286581728 |
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| 100 | 1 | |a Wang, Luwen |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Mitofusin 2 Regulates Axonal Transport of Calpastatin to Prevent Neuromuscular Synaptic Elimination in Skeletal Muscles |
| 264 | 1 | |c 2018 | |
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| 500 | |a CommentIn: Cell Metab. 2018 Oct 2;28(4):536-538. - PMID 30282045 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2018 Elsevier Inc. All rights reserved. | ||
| 520 | |a Skeletal muscles undergo atrophy in response to diseases and aging. Here we report that mitofusin 2 (Mfn2) acts as a dominant suppressor of neuromuscular synaptic loss to preserve skeletal muscles. Mfn2 is reduced in spinal cords of transgenic SOD1G93A and aged mice. Through preserving neuromuscular synapses, increasing neuronal Mfn2 prevents skeletal muscle wasting in both SOD1G93A and aged mice, whereas deletion of neuronal Mfn2 produces neuromuscular synaptic dysfunction and skeletal muscle atrophy. Neuromuscular synaptic loss after sciatic nerve transection can also be alleviated by Mfn2. Mfn2 coexists with calpastatin largely in mitochondria-associated membranes (MAMs) to regulate its axonal transport. Genetic inactivation of calpastatin abolishes Mfn2-mediated protection of neuromuscular synapses. Our results suggest that, as a potential key component of a novel and heretofore unrecognized mechanism of cytoplasmic protein transport, Mfn2 may play a general role in preserving neuromuscular synapses and serve as a common therapeutic target for skeletal muscle atrophy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Mfn2 | |
| 650 | 4 | |a amyotrophic lateral sclerosis | |
| 650 | 4 | |a axonal transport | |
| 650 | 4 | |a calpastatin | |
| 650 | 4 | |a mitochondria | |
| 650 | 4 | |a mitochondria-associated membranes | |
| 650 | 4 | |a nerve injury | |
| 650 | 4 | |a neuromuscular synapse | |
| 650 | 4 | |a sarcopenia | |
| 650 | 4 | |a skeletal muscle atrophy | |
| 650 | 7 | |a Calcium-Binding Proteins |2 NLM | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 650 | 7 | |a Mitochondrial Proteins |2 NLM | |
| 650 | 7 | |a calpastatin |2 NLM | |
| 650 | 7 | |a 79079-11-1 |2 NLM | |
| 650 | 7 | |a GTP Phosphohydrolases |2 NLM | |
| 650 | 7 | |a EC 3.6.1.- |2 NLM | |
| 650 | 7 | |a Mfn2 protein, mouse |2 NLM | |
| 650 | 7 | |a EC 3.6.1.- |2 NLM | |
| 700 | 1 | |a Gao, Ju |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jingyi |e verfasserin |4 aut | |
| 700 | 1 | |a Siedlak, Sandra L |e verfasserin |4 aut | |
| 700 | 1 | |a Torres, Sandy |e verfasserin |4 aut | |
| 700 | 1 | |a Fujioka, Hisashi |e verfasserin |4 aut | |
| 700 | 1 | |a Huntley, Mikayla L |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Yinfei |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, Haiyan |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Tingxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Harland, Micah |e verfasserin |4 aut | |
| 700 | 1 | |a Termsarasab, Pichet |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Sophia |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Jingjing |e verfasserin |4 aut | |
| 700 | 1 | |a Perry, George |e verfasserin |4 aut | |
| 700 | 1 | |a Hoppel, Charles |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xinglong |e verfasserin |4 aut | |
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