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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2019
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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. |
format | Online Article Text |
id | pubmed-6337907 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT irajizadehsan geometricinstabilitycatalyzesmitochondrialfission AT ramachandranrajesh geometricinstabilitycatalyzesmitochondrialfission AT agrawalashutosh geometricinstabilitycatalyzesmitochondrialfission |