Resting mitochondrial complex I from Drosophila melanogaster adopts a helix-locked state
Respiratory complex I is a proton-pumping oxidoreductase key to bioenergetic metabolism. Biochemical studies have found a divide in the behavior of complex I in metazoans that aligns with the evolutionary split between Protostomia and Deuterostomia. Complex I from Deuterostomia including mammals can...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/84415 |
| _version_ | 1797861368781602816 |
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| author | Abhilash Padavannil Anjaneyulu Murari Shauna-Kay Rhooms Edward Owusu-Ansah James A Letts |
| author_facet | Abhilash Padavannil Anjaneyulu Murari Shauna-Kay Rhooms Edward Owusu-Ansah James A Letts |
| author_sort | Abhilash Padavannil |
| collection | DOAJ |
| description | Respiratory complex I is a proton-pumping oxidoreductase key to bioenergetic metabolism. Biochemical studies have found a divide in the behavior of complex I in metazoans that aligns with the evolutionary split between Protostomia and Deuterostomia. Complex I from Deuterostomia including mammals can adopt a biochemically defined off-pathway ‘deactive’ state, whereas complex I from Protostomia cannot. The presence of off-pathway states complicates the interpretation of structural results and has led to considerable mechanistic debate. Here, we report the structure of mitochondrial complex I from the thoracic muscles of the model protostome Drosophila melanogaster. We show that although D. melanogaster complex I (Dm-CI) does not have a NEM-sensitive deactive state, it does show slow activation kinetics indicative of an off-pathway resting state. The resting-state structure of Dm-CI from the thoracic muscle reveals multiple conformations. We identify a helix-locked state in which an N-terminal α-helix on the NDUFS4 subunit wedges between the peripheral and membrane arms. Comparison of the Dm-CI structure and conformational states to those observed in bacteria, yeast, and mammals provides insight into the roles of subunits across organisms, explains why the Dm-CI off-pathway resting state is NEM insensitive, and raises questions regarding current mechanistic models of complex I turnover. |
| first_indexed | 2024-04-09T22:02:26Z |
| format | Article |
| id | doaj.art-aa79db567dd941b0920c1e43136c1572 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-09T22:02:26Z |
| publishDate | 2023-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-aa79db567dd941b0920c1e43136c15722023-03-23T17:19:08ZengeLife Sciences Publications LtdeLife2050-084X2023-03-011210.7554/eLife.84415Resting mitochondrial complex I from Drosophila melanogaster adopts a helix-locked stateAbhilash Padavannil0https://orcid.org/0000-0002-9949-6776Anjaneyulu Murari1https://orcid.org/0000-0002-7532-964XShauna-Kay Rhooms2Edward Owusu-Ansah3https://orcid.org/0000-0002-3451-1752James A Letts4https://orcid.org/0000-0002-9864-3586Department of Molecular and Cellular Biology, University of California, Davis, Davis, United StatesDepartment of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, United StatesDepartment of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, United StatesDepartment of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, United States; The Robert N. Butler Columbia Aging Center, Columbia University Irving Medical Center, New York, United StatesDepartment of Molecular and Cellular Biology, University of California, Davis, Davis, United StatesRespiratory complex I is a proton-pumping oxidoreductase key to bioenergetic metabolism. Biochemical studies have found a divide in the behavior of complex I in metazoans that aligns with the evolutionary split between Protostomia and Deuterostomia. Complex I from Deuterostomia including mammals can adopt a biochemically defined off-pathway ‘deactive’ state, whereas complex I from Protostomia cannot. The presence of off-pathway states complicates the interpretation of structural results and has led to considerable mechanistic debate. Here, we report the structure of mitochondrial complex I from the thoracic muscles of the model protostome Drosophila melanogaster. We show that although D. melanogaster complex I (Dm-CI) does not have a NEM-sensitive deactive state, it does show slow activation kinetics indicative of an off-pathway resting state. The resting-state structure of Dm-CI from the thoracic muscle reveals multiple conformations. We identify a helix-locked state in which an N-terminal α-helix on the NDUFS4 subunit wedges between the peripheral and membrane arms. Comparison of the Dm-CI structure and conformational states to those observed in bacteria, yeast, and mammals provides insight into the roles of subunits across organisms, explains why the Dm-CI off-pathway resting state is NEM insensitive, and raises questions regarding current mechanistic models of complex I turnover.https://elifesciences.org/articles/84415mitochondriacomplex Isingle particle cryoEMelectron transport chainrespiration |
| spellingShingle | Abhilash Padavannil Anjaneyulu Murari Shauna-Kay Rhooms Edward Owusu-Ansah James A Letts Resting mitochondrial complex I from Drosophila melanogaster adopts a helix-locked state eLife mitochondria complex I single particle cryoEM electron transport chain respiration |
| title | Resting mitochondrial complex I from Drosophila melanogaster adopts a helix-locked state |
| title_full | Resting mitochondrial complex I from Drosophila melanogaster adopts a helix-locked state |
| title_fullStr | Resting mitochondrial complex I from Drosophila melanogaster adopts a helix-locked state |
| title_full_unstemmed | Resting mitochondrial complex I from Drosophila melanogaster adopts a helix-locked state |
| title_short | Resting mitochondrial complex I from Drosophila melanogaster adopts a helix-locked state |
| title_sort | resting mitochondrial complex i from drosophila melanogaster adopts a helix locked state |
| topic | mitochondria complex I single particle cryoEM electron transport chain respiration |
| url | https://elifesciences.org/articles/84415 |
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