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Ups1p and Ups2p antagonistically regulate cardiolipin metabolism in mitochondria
Cardiolipin, a unique phospholipid composed of four fatty acid chains, is located mainly in the mitochondrial inner membrane (IM). Cardiolipin is required for the integrity of several protein complexes in the IM, including the TIM23 translocase, a dynamic complex which mediates protein import into t...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711612/ https://www.ncbi.nlm.nih.gov/pubmed/19506038 http://dx.doi.org/10.1083/jcb.200812018 |
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author | Tamura, Yasushi Endo, Toshiya Iijima, Miho Sesaki, Hiromi |
author_facet | Tamura, Yasushi Endo, Toshiya Iijima, Miho Sesaki, Hiromi |
author_sort | Tamura, Yasushi |
collection | PubMed |
description | Cardiolipin, a unique phospholipid composed of four fatty acid chains, is located mainly in the mitochondrial inner membrane (IM). Cardiolipin is required for the integrity of several protein complexes in the IM, including the TIM23 translocase, a dynamic complex which mediates protein import into the mitochondria through interactions with the import motor presequence translocase–associated motor (PAM). In this study, we report that two homologous intermembrane space proteins, Ups1p and Ups2p, control cardiolipin metabolism and affect the assembly state of TIM23 and its association with PAM in an opposing manner. In ups1Δ mitochondria, cardiolipin levels were decreased, and the TIM23 translocase showed altered conformation and decreased association with PAM, leading to defects in mitochondrial protein import. Strikingly, loss of Ups2p restored normal cardiolipin levels and rescued TIM23 defects in ups1Δ mitochondria. Furthermore, we observed synthetic growth defects in ups mutants in combination with loss of Pam17p, which controls the integrity of PAM. Our findings provide a novel molecular mechanism for the regulation of cardiolipin metabolism. |
format | Text |
id | pubmed-2711612 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-27116122009-12-15 Ups1p and Ups2p antagonistically regulate cardiolipin metabolism in mitochondria Tamura, Yasushi Endo, Toshiya Iijima, Miho Sesaki, Hiromi J Cell Biol Research Articles Cardiolipin, a unique phospholipid composed of four fatty acid chains, is located mainly in the mitochondrial inner membrane (IM). Cardiolipin is required for the integrity of several protein complexes in the IM, including the TIM23 translocase, a dynamic complex which mediates protein import into the mitochondria through interactions with the import motor presequence translocase–associated motor (PAM). In this study, we report that two homologous intermembrane space proteins, Ups1p and Ups2p, control cardiolipin metabolism and affect the assembly state of TIM23 and its association with PAM in an opposing manner. In ups1Δ mitochondria, cardiolipin levels were decreased, and the TIM23 translocase showed altered conformation and decreased association with PAM, leading to defects in mitochondrial protein import. Strikingly, loss of Ups2p restored normal cardiolipin levels and rescued TIM23 defects in ups1Δ mitochondria. Furthermore, we observed synthetic growth defects in ups mutants in combination with loss of Pam17p, which controls the integrity of PAM. Our findings provide a novel molecular mechanism for the regulation of cardiolipin metabolism. The Rockefeller University Press 2009-06-15 /pmc/articles/PMC2711612/ /pubmed/19506038 http://dx.doi.org/10.1083/jcb.200812018 Text en © 2009 Tamura 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.jcb.org/misc/terms.shtml). 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 Tamura, Yasushi Endo, Toshiya Iijima, Miho Sesaki, Hiromi Ups1p and Ups2p antagonistically regulate cardiolipin metabolism in mitochondria |
title | Ups1p and Ups2p antagonistically regulate cardiolipin metabolism in mitochondria |
title_full | Ups1p and Ups2p antagonistically regulate cardiolipin metabolism in mitochondria |
title_fullStr | Ups1p and Ups2p antagonistically regulate cardiolipin metabolism in mitochondria |
title_full_unstemmed | Ups1p and Ups2p antagonistically regulate cardiolipin metabolism in mitochondria |
title_short | Ups1p and Ups2p antagonistically regulate cardiolipin metabolism in mitochondria |
title_sort | ups1p and ups2p antagonistically regulate cardiolipin metabolism in mitochondria |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711612/ https://www.ncbi.nlm.nih.gov/pubmed/19506038 http://dx.doi.org/10.1083/jcb.200812018 |
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