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Identification of a mitofusin specificity region that confers unique activities to Mfn1 and Mfn2

Mitochondrial structure can be maintained at steady state or modified in response to changes in cellular physiology. This is achieved by the coordinated regulation of dynamic properties including mitochondrial fusion, division, and transport. Disease states, including neurodegeneration, are associat...

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Autores principales: Sloat, S. R., Whitley, B. N., Engelhart, E. A., Hoppins, S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743458/
https://www.ncbi.nlm.nih.gov/pubmed/31188717
http://dx.doi.org/10.1091/mbc.E19-05-0291
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author Sloat, S. R.
Whitley, B. N.
Engelhart, E. A.
Hoppins, S.
author_facet Sloat, S. R.
Whitley, B. N.
Engelhart, E. A.
Hoppins, S.
author_sort Sloat, S. R.
collection PubMed
description Mitochondrial structure can be maintained at steady state or modified in response to changes in cellular physiology. This is achieved by the coordinated regulation of dynamic properties including mitochondrial fusion, division, and transport. Disease states, including neurodegeneration, are associated with defects in these processes. In vertebrates, two mitofusin paralogues, Mfn1 and Mfn2, are required for efficient mitochondrial fusion. The mitofusins share a high degree of homology and have very similar domain architecture, including an amino terminal GTPase domain and two extended helical bundles that are connected by flexible regions. Mfn1 and Mfn2 are nonredundant and are both required for mitochondrial outer membrane fusion. However, the molecular features that make these proteins functionally distinct are poorly defined. By engineering chimeric proteins composed of Mfn1 and Mfn2, we discovered a region that contributes to isoform-specific function (mitofusin isoform-specific region [MISR]). MISR confers unique fusion activity and mitofusin-specific nucleotide-dependent assembly properties. We propose that MISR functions in higher-order oligomerization either directly, as an interaction interface, or indirectly through conformational changes.
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spelling pubmed-67434582019-10-16 Identification of a mitofusin specificity region that confers unique activities to Mfn1 and Mfn2 Sloat, S. R. Whitley, B. N. Engelhart, E. A. Hoppins, S. Mol Biol Cell Articles Mitochondrial structure can be maintained at steady state or modified in response to changes in cellular physiology. This is achieved by the coordinated regulation of dynamic properties including mitochondrial fusion, division, and transport. Disease states, including neurodegeneration, are associated with defects in these processes. In vertebrates, two mitofusin paralogues, Mfn1 and Mfn2, are required for efficient mitochondrial fusion. The mitofusins share a high degree of homology and have very similar domain architecture, including an amino terminal GTPase domain and two extended helical bundles that are connected by flexible regions. Mfn1 and Mfn2 are nonredundant and are both required for mitochondrial outer membrane fusion. However, the molecular features that make these proteins functionally distinct are poorly defined. By engineering chimeric proteins composed of Mfn1 and Mfn2, we discovered a region that contributes to isoform-specific function (mitofusin isoform-specific region [MISR]). MISR confers unique fusion activity and mitofusin-specific nucleotide-dependent assembly properties. We propose that MISR functions in higher-order oligomerization either directly, as an interaction interface, or indirectly through conformational changes. The American Society for Cell Biology 2019-08-01 /pmc/articles/PMC6743458/ /pubmed/31188717 http://dx.doi.org/10.1091/mbc.E19-05-0291 Text en © 2019 Sloat et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Articles
Sloat, S. R.
Whitley, B. N.
Engelhart, E. A.
Hoppins, S.
Identification of a mitofusin specificity region that confers unique activities to Mfn1 and Mfn2
title Identification of a mitofusin specificity region that confers unique activities to Mfn1 and Mfn2
title_full Identification of a mitofusin specificity region that confers unique activities to Mfn1 and Mfn2
title_fullStr Identification of a mitofusin specificity region that confers unique activities to Mfn1 and Mfn2
title_full_unstemmed Identification of a mitofusin specificity region that confers unique activities to Mfn1 and Mfn2
title_short Identification of a mitofusin specificity region that confers unique activities to Mfn1 and Mfn2
title_sort identification of a mitofusin specificity region that confers unique activities to mfn1 and mfn2
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743458/
https://www.ncbi.nlm.nih.gov/pubmed/31188717
http://dx.doi.org/10.1091/mbc.E19-05-0291
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