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Geometric instability catalyzes mitochondrial fission

The mitochondrial membrane undergoes extreme remodeling during fission. While a few membrane-squeezing proteins are recognized as the key drivers of fission, there is a growing body of evidence that strongly suggests that conical lipids play a critical role in regulating mitochondrial morphology and...

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Detalles Bibliográficos
Autores principales: Irajizad, Ehsan, Ramachandran, Rajesh, Agrawal, Ashutosh
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/PMC6337907/
https://www.ncbi.nlm.nih.gov/pubmed/30379601
http://dx.doi.org/10.1091/mbc.E18-01-0018
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author Irajizad, Ehsan
Ramachandran, Rajesh
Agrawal, Ashutosh
author_facet Irajizad, Ehsan
Ramachandran, Rajesh
Agrawal, Ashutosh
author_sort Irajizad, Ehsan
collection PubMed
description The mitochondrial membrane undergoes extreme remodeling during fission. While a few membrane-squeezing proteins are recognized as the key drivers of fission, there is a growing body of evidence that strongly suggests that conical lipids play a critical role in regulating mitochondrial morphology and fission. However, the mechanisms by which proteins and lipids cooperate to execute fission have not been quantitatively investigated. Here, we computationally model the squeezing of the largely tubular mitochondrion and show that proteins and conical lipids can act synergistically to trigger buckling instability and achieve extreme constriction. More remarkably, the study reveals that the conical lipids can act with different fission proteins to induce hierarchical instabilities and create increasingly narrow and stable constrictions. We reason that this geometric plasticity imparts significant robustness to the fission reaction by arresting the elastic tendency of the membrane to rebound during protein polymerization and depolymerization cycles. Our in vitro study validates protein–lipid cooperativity in constricting membrane tubules. Overall, our work presents a general mechanism for achieving drastic topological remodeling in cellular membranes.
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spelling pubmed-63379072019-03-16 Geometric instability catalyzes mitochondrial fission Irajizad, Ehsan Ramachandran, Rajesh Agrawal, Ashutosh Mol Biol Cell Articles The mitochondrial membrane undergoes extreme remodeling during fission. While a few membrane-squeezing proteins are recognized as the key drivers of fission, there is a growing body of evidence that strongly suggests that conical lipids play a critical role in regulating mitochondrial morphology and fission. However, the mechanisms by which proteins and lipids cooperate to execute fission have not been quantitatively investigated. Here, we computationally model the squeezing of the largely tubular mitochondrion and show that proteins and conical lipids can act synergistically to trigger buckling instability and achieve extreme constriction. More remarkably, the study reveals that the conical lipids can act with different fission proteins to induce hierarchical instabilities and create increasingly narrow and stable constrictions. We reason that this geometric plasticity imparts significant robustness to the fission reaction by arresting the elastic tendency of the membrane to rebound during protein polymerization and depolymerization cycles. Our in vitro study validates protein–lipid cooperativity in constricting membrane tubules. Overall, our work presents a general mechanism for achieving drastic topological remodeling in cellular membranes. The American Society for Cell Biology 2019-01-01 /pmc/articles/PMC6337907/ /pubmed/30379601 http://dx.doi.org/10.1091/mbc.E18-01-0018 Text en © 2019 Irajizad 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
Irajizad, Ehsan
Ramachandran, Rajesh
Agrawal, Ashutosh
Geometric instability catalyzes mitochondrial fission
title Geometric instability catalyzes mitochondrial fission
title_full Geometric instability catalyzes mitochondrial fission
title_fullStr Geometric instability catalyzes mitochondrial fission
title_full_unstemmed Geometric instability catalyzes mitochondrial fission
title_short Geometric instability catalyzes mitochondrial fission
title_sort geometric instability catalyzes mitochondrial fission
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337907/
https://www.ncbi.nlm.nih.gov/pubmed/30379601
http://dx.doi.org/10.1091/mbc.E18-01-0018
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AT ramachandranrajesh geometricinstabilitycatalyzesmitochondrialfission
AT agrawalashutosh geometricinstabilitycatalyzesmitochondrialfission