Subcomplex Ilambda specifically controls integrated mitochondrial functions in Caenorhabditis elegans.
Complex I dysfunction is a common, heterogeneous cause of human mitochondrial disease having poorly understood pathogenesis. The extensive conservation of complex I composition between humans and Caenorhabditis elegans permits analysis of individual subunit contribution to mitochondrial functions at...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-08-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2719872?pdf=render |
| _version_ | 1818250834384781312 |
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| author | Marni J Falk Julie R Rosenjack Erzsebet Polyak Wichit Suthammarak Zhongxue Chen Phil G Morgan Margaret M Sedensky |
| author_facet | Marni J Falk Julie R Rosenjack Erzsebet Polyak Wichit Suthammarak Zhongxue Chen Phil G Morgan Margaret M Sedensky |
| author_sort | Marni J Falk |
| collection | DOAJ |
| description | Complex I dysfunction is a common, heterogeneous cause of human mitochondrial disease having poorly understood pathogenesis. The extensive conservation of complex I composition between humans and Caenorhabditis elegans permits analysis of individual subunit contribution to mitochondrial functions at both the whole animal and mitochondrial levels. We provide the first experimentally-verified compilation of complex I composition in C. elegans, demonstrating 84% conservation with human complex I. Individual subunit contribution to mitochondrial respiratory capacity, holocomplex I assembly, and animal anesthetic behavior was studied in C. elegans by RNA interference-generated knockdown of nuclear genes encoding 28 complex I structural subunits and 2 assembly factors. Not all complex I subunits directly impact respiratory capacity. Subcomplex Ilambda subunits along the electron transfer pathway specifically control whole animal anesthetic sensitivity and complex II upregulation, proportionate to their relative impairment of complex I-dependent oxidative capacity. Translational analysis of complex I dysfunction facilitates mechanistic understanding of individual gene contribution to mitochondrial disease. We demonstrate that functional consequences of complex I deficiency vary with the particular subunit that is defective. |
| first_indexed | 2024-12-12T15:58:41Z |
| format | Article |
| id | doaj.art-ce4e7d1444054ec687394637313a46a5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T15:58:41Z |
| publishDate | 2009-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ce4e7d1444054ec687394637313a46a52022-12-22T00:19:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-08-0148e660710.1371/journal.pone.0006607Subcomplex Ilambda specifically controls integrated mitochondrial functions in Caenorhabditis elegans.Marni J FalkJulie R RosenjackErzsebet PolyakWichit SuthammarakZhongxue ChenPhil G MorganMargaret M SedenskyComplex I dysfunction is a common, heterogeneous cause of human mitochondrial disease having poorly understood pathogenesis. The extensive conservation of complex I composition between humans and Caenorhabditis elegans permits analysis of individual subunit contribution to mitochondrial functions at both the whole animal and mitochondrial levels. We provide the first experimentally-verified compilation of complex I composition in C. elegans, demonstrating 84% conservation with human complex I. Individual subunit contribution to mitochondrial respiratory capacity, holocomplex I assembly, and animal anesthetic behavior was studied in C. elegans by RNA interference-generated knockdown of nuclear genes encoding 28 complex I structural subunits and 2 assembly factors. Not all complex I subunits directly impact respiratory capacity. Subcomplex Ilambda subunits along the electron transfer pathway specifically control whole animal anesthetic sensitivity and complex II upregulation, proportionate to their relative impairment of complex I-dependent oxidative capacity. Translational analysis of complex I dysfunction facilitates mechanistic understanding of individual gene contribution to mitochondrial disease. We demonstrate that functional consequences of complex I deficiency vary with the particular subunit that is defective.http://europepmc.org/articles/PMC2719872?pdf=render |
| spellingShingle | Marni J Falk Julie R Rosenjack Erzsebet Polyak Wichit Suthammarak Zhongxue Chen Phil G Morgan Margaret M Sedensky Subcomplex Ilambda specifically controls integrated mitochondrial functions in Caenorhabditis elegans. PLoS ONE |
| title | Subcomplex Ilambda specifically controls integrated mitochondrial functions in Caenorhabditis elegans. |
| title_full | Subcomplex Ilambda specifically controls integrated mitochondrial functions in Caenorhabditis elegans. |
| title_fullStr | Subcomplex Ilambda specifically controls integrated mitochondrial functions in Caenorhabditis elegans. |
| title_full_unstemmed | Subcomplex Ilambda specifically controls integrated mitochondrial functions in Caenorhabditis elegans. |
| title_short | Subcomplex Ilambda specifically controls integrated mitochondrial functions in Caenorhabditis elegans. |
| title_sort | subcomplex ilambda specifically controls integrated mitochondrial functions in caenorhabditis elegans |
| url | http://europepmc.org/articles/PMC2719872?pdf=render |
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