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MICOS and phospholipid transfer by Ups2–Mdm35 organize membrane lipid synthesis in mitochondria
Mitochondria exert critical functions in cellular lipid metabolism and promote the synthesis of major constituents of cellular membranes, such as phosphatidylethanolamine (PE) and phosphatidylcholine. Here, we demonstrate that the phosphatidylserine decarboxylase Psd1, located in the inner mitochond...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896057/ https://www.ncbi.nlm.nih.gov/pubmed/27241913 http://dx.doi.org/10.1083/jcb.201602007 |
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author | Aaltonen, Mari J. Friedman, Jonathan R. Osman, Christof Salin, Bénédicte di Rago, Jean-Paul Nunnari, Jodi Langer, Thomas Tatsuta, Takashi |
author_facet | Aaltonen, Mari J. Friedman, Jonathan R. Osman, Christof Salin, Bénédicte di Rago, Jean-Paul Nunnari, Jodi Langer, Thomas Tatsuta, Takashi |
author_sort | Aaltonen, Mari J. |
collection | PubMed |
description | Mitochondria exert critical functions in cellular lipid metabolism and promote the synthesis of major constituents of cellular membranes, such as phosphatidylethanolamine (PE) and phosphatidylcholine. Here, we demonstrate that the phosphatidylserine decarboxylase Psd1, located in the inner mitochondrial membrane, promotes mitochondrial PE synthesis via two pathways. First, Ups2–Mdm35 complexes (SLMO2–TRIAP1 in humans) serve as phosphatidylserine (PS)-specific lipid transfer proteins in the mitochondrial intermembrane space, allowing formation of PE by Psd1 in the inner membrane. Second, Psd1 decarboxylates PS in the outer membrane in trans, independently of PS transfer by Ups2–Mdm35. This latter pathway requires close apposition between both mitochondrial membranes and the mitochondrial contact site and cristae organizing system (MICOS). In MICOS-deficient cells, limiting PS transfer by Ups2–Mdm35 and reducing mitochondrial PE accumulation preserves mitochondrial respiration and cristae formation. These results link mitochondrial PE metabolism to MICOS, combining functions in protein and lipid homeostasis to preserve mitochondrial structure and function. |
format | Online Article Text |
id | pubmed-4896057 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-48960572016-12-06 MICOS and phospholipid transfer by Ups2–Mdm35 organize membrane lipid synthesis in mitochondria Aaltonen, Mari J. Friedman, Jonathan R. Osman, Christof Salin, Bénédicte di Rago, Jean-Paul Nunnari, Jodi Langer, Thomas Tatsuta, Takashi J Cell Biol Research Articles Mitochondria exert critical functions in cellular lipid metabolism and promote the synthesis of major constituents of cellular membranes, such as phosphatidylethanolamine (PE) and phosphatidylcholine. Here, we demonstrate that the phosphatidylserine decarboxylase Psd1, located in the inner mitochondrial membrane, promotes mitochondrial PE synthesis via two pathways. First, Ups2–Mdm35 complexes (SLMO2–TRIAP1 in humans) serve as phosphatidylserine (PS)-specific lipid transfer proteins in the mitochondrial intermembrane space, allowing formation of PE by Psd1 in the inner membrane. Second, Psd1 decarboxylates PS in the outer membrane in trans, independently of PS transfer by Ups2–Mdm35. This latter pathway requires close apposition between both mitochondrial membranes and the mitochondrial contact site and cristae organizing system (MICOS). In MICOS-deficient cells, limiting PS transfer by Ups2–Mdm35 and reducing mitochondrial PE accumulation preserves mitochondrial respiration and cristae formation. These results link mitochondrial PE metabolism to MICOS, combining functions in protein and lipid homeostasis to preserve mitochondrial structure and function. The Rockefeller University Press 2016-06-06 /pmc/articles/PMC4896057/ /pubmed/27241913 http://dx.doi.org/10.1083/jcb.201602007 Text en © 2016 Aaltonen et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Aaltonen, Mari J. Friedman, Jonathan R. Osman, Christof Salin, Bénédicte di Rago, Jean-Paul Nunnari, Jodi Langer, Thomas Tatsuta, Takashi MICOS and phospholipid transfer by Ups2–Mdm35 organize membrane lipid synthesis in mitochondria |
title | MICOS and phospholipid transfer by Ups2–Mdm35 organize membrane lipid synthesis in mitochondria |
title_full | MICOS and phospholipid transfer by Ups2–Mdm35 organize membrane lipid synthesis in mitochondria |
title_fullStr | MICOS and phospholipid transfer by Ups2–Mdm35 organize membrane lipid synthesis in mitochondria |
title_full_unstemmed | MICOS and phospholipid transfer by Ups2–Mdm35 organize membrane lipid synthesis in mitochondria |
title_short | MICOS and phospholipid transfer by Ups2–Mdm35 organize membrane lipid synthesis in mitochondria |
title_sort | micos and phospholipid transfer by ups2–mdm35 organize membrane lipid synthesis in mitochondria |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896057/ https://www.ncbi.nlm.nih.gov/pubmed/27241913 http://dx.doi.org/10.1083/jcb.201602007 |
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