Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A.
Stephan Züchner,Stephan Züchner,Irina V. Mersiyanova,Maria Muglia,Nisrine Bissar-Tadmouri,Nisrine Bissar-Tadmouri,Julie M. Rochelle,Elena L. Dadali,Mario Zappia,Eva Nelis,Alessandra Patitucci,Jan Senderek,Yesim Parman,Oleg V. Evgrafov,Peter De Jonghe,Yuji Takahashi,Shoij Tsuji,Margaret A. Pericak-Vance,Aldo Quattrone,Esra Battologlu,Alexander V. Polyakov,Vincent Timmerman,J. Michael Schröder,Jeffery M. Vance +23 more
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TLDR
It is concluded that the primary gene mutated in CMT2A is MFN2, and seven large pedigrees affected with Charcot-Marie-Tooth neuropathy type 2A are concluded.Abstract:
We report missense mutations in the mitochondrial fusion protein mitofusin 2 (MFN2) in seven large pedigrees affected with Charcot-Marie-Tooth neuropathy type 2A (CMT2A). Although a mutation in kinesin family member 1B-β (KIF1B) was associated with CMT2A in a single Japanese family, we found no mutations in KIF1B in these seven families. Because these families include all published pedigrees with CMT2A and are ethnically diverse, we conclude that the primary gene mutated in CMT2A is MFN2.read more
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Mitochondria: In Sickness and in Health
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Mitofusin 2 tethers endoplasmic reticulum to mitochondria
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TL;DR: The core components of the evolutionarily conserved fusion and fission machineries have now been identified, and mechanistic studies have revealed the first secrets of the complex processes that govern fusion andfission of a double membrane-bound organelle.
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Mitochondrial dynamics–fusion, fission, movement, and mitophagy–in neurodegenerative diseases
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References
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Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development
TL;DR: It is concluded that Mfn1 and Mfn2 have both redundant and distinct functions and act in three separate molecular complexes to promote mitochondrial fusion, and by enabling cooperation between mitochondria, has protective effects on the mitochondrial population.
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Control of mitochondrial morphology by a human mitofusin
Ansgar Santel,Margaret T. Fuller +1 more
TL;DR: Two human genes encoding potential mediators of mitochondrial fusion are identified and it is suggested that the Mfn2 GTPase regulates or mediates mitochondrial fusion and that mitofusins and dynamin related GTPases play opposing roles in mitochondria fusion and fission in mammals, as in yeast.
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Spatial and temporal association of Bax with mitochondrial fission sites, Drp1, and Mfn2 during apoptosis
Mariusz Karbowski,Yang-Ja Lee,Brigitte Gaume,Seon-Yong Jeong,Stephan Frank,Amotz Nechushtan,Ansgar Santel,Margaret T. Fuller,Carolyn L. Smith,Richard J. Youle +9 more
TL;DR: It is suggested that Bax participates in apoptotic fragmentation of mitochondria, a proapoptotic member of the Bcl-2 family that translocates to discrete foci on mitochondria during the initial stages of apoptosis, which subsequently become mitochondrial scission sites.
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Mitofusin-2 Determines Mitochondrial Network Architecture and Mitochondrial Metabolism A NOVEL REGULATORY MECHANISM ALTERED IN OBESITY
Daniel Bach,Sara Pich,Francesc X. Soriano,Nathalie Vega,Bernhard Baumgartner,Josep Oriola,Jens R. Daugaard,Jorge Lloberas,Marta Camps,Juleen R. Zierath,Rémi Rabasa-Lhoret,Harriet Wallberg-Henriksson,Martine Laville,Manuel Palacín,Hubert Vidal,Francisca Rivera,Martin D. Brand,Antonio Zorzano +17 more
TL;DR: It is shown that Mfn2 (mitofusin 2), a mitochondrial membrane protein that participates in mitochondrial fusion in mammalian cells, is induced during myogenesis and contributes to the maintenance and operation of the mitochondrial network.
Journal ArticleDOI
Charcot-Marie-Tooth Disease Type 2A Caused by Mutation in a Microtubule Motor KIF1Bβ
Chunjie Zhao,Junko Takita,Yosuke Tanaka,Mitsutoshi Setou,Terunaga Nakagawa,Sen Takeda,Hongwei Yang,Sumio Terada,Takao Nakata,Yosuke Takei,Masaaki Saito,Shoji Tsuji,Yasuhide Hayashi,Nobutaka Hirokawa +13 more
TL;DR: It is shown that CMT2A patients contain a loss-of-function mutation in the motor domain of the KIF1B gene, clear indication that defects in axonal transport due to a mutated motor protein can underlie human peripheral neuropathy.