Assembly of the complexes of oxidative phosphorylation triggers the remodeling of cardiolipin
Cardiolipin (CL) is a mitochondrial phospholipid with a very specific and functionally important fatty acid composition, generated by tafazzin. However, in vitro tafazzin catalyzes a promiscuous acyl exchange that acquires specificity only in response to perturbations of the physical state of lipids. To identify the process that imposes acyl specificity onto CL remodeling in vivo, we analyzed a series of deletions and knockdowns in Saccharomyces cerevisiae and Drosophila melanogaster, including carriers, membrane homeostasis proteins, fission-fusion proteins, cristae-shape controlling and MICOS proteins, and the complexes I-V. Among those, only the complexes of oxidative phosphorylation (OXPHOS) affected the CL composition. Rather than any specific complex, it was the global impairment of the OXPHOS system that altered CL and at the same time shortened its half-life. The knockdown of OXPHOS expression had the same effect on CL as the knockdown of tafazzin in Drosophila flight muscles, including a change in CL composition and the accumulation of monolyso-CL. Thus, the assembly of OXPHOS complexes induces CL remodeling, which, in turn, leads to CL stabilization. We hypothesize that protein crowding in the OXPHOS system imposes packing stress on the lipid bilayer, which is relieved by CL remodeling to form tightly packed lipid-protein complexes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:116 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 116(2019), 23 vom: 04. Juni, Seite 11235-11240 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xu, Yang [VerfasserIn] |
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| Links: |
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| Themen: |
Cardiolipin |
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| Anmerkungen: |
Date Completed 25.03.2020 Date Revised 25.03.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1073/pnas.1900890116 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM297284614 |
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| 245 | 1 | 0 | |a Assembly of the complexes of oxidative phosphorylation triggers the remodeling of cardiolipin |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Cardiolipin (CL) is a mitochondrial phospholipid with a very specific and functionally important fatty acid composition, generated by tafazzin. However, in vitro tafazzin catalyzes a promiscuous acyl exchange that acquires specificity only in response to perturbations of the physical state of lipids. To identify the process that imposes acyl specificity onto CL remodeling in vivo, we analyzed a series of deletions and knockdowns in Saccharomyces cerevisiae and Drosophila melanogaster, including carriers, membrane homeostasis proteins, fission-fusion proteins, cristae-shape controlling and MICOS proteins, and the complexes I-V. Among those, only the complexes of oxidative phosphorylation (OXPHOS) affected the CL composition. Rather than any specific complex, it was the global impairment of the OXPHOS system that altered CL and at the same time shortened its half-life. The knockdown of OXPHOS expression had the same effect on CL as the knockdown of tafazzin in Drosophila flight muscles, including a change in CL composition and the accumulation of monolyso-CL. Thus, the assembly of OXPHOS complexes induces CL remodeling, which, in turn, leads to CL stabilization. We hypothesize that protein crowding in the OXPHOS system imposes packing stress on the lipid bilayer, which is relieved by CL remodeling to form tightly packed lipid-protein complexes | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a cardiolipin | |
| 650 | 4 | |a lipids | |
| 650 | 4 | |a membrane | |
| 650 | 4 | |a mitochondria | |
| 650 | 4 | |a respiration | |
| 650 | 7 | |a Cardiolipins |2 NLM | |
| 650 | 7 | |a Lipid Bilayers |2 NLM | |
| 650 | 7 | |a Phospholipids |2 NLM | |
| 650 | 7 | |a Saccharomyces cerevisiae Proteins |2 NLM | |
| 700 | 1 | |a Anjaneyulu, Murari |e verfasserin |4 aut | |
| 700 | 1 | |a Donelian, Alec |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Wenxi |e verfasserin |4 aut | |
| 700 | 1 | |a Greenberg, Miriam L |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Mindong |e verfasserin |4 aut | |
| 700 | 1 | |a Owusu-Ansah, Edward |e verfasserin |4 aut | |
| 700 | 1 | |a Schlame, Michael |e verfasserin |4 aut | |
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