---
_id: '1226'
abstract:
- lang: eng
text: Mitochondrial complex I (also known as NADH:ubiquinone oxidoreductase) contributes
to cellular energy production by transferring electrons from NADH to ubiquinone
coupled to proton translocation across the membrane. It is the largest protein
assembly of the respiratory chain with a total mass of 970 kilodaltons. Here we
present a nearly complete atomic structure of ovine (Ovis aries) mitochondrial
complex I at 3.9 Å resolution, solved by cryo-electron microscopy with cross-linking
and mass-spectrometry mapping experiments. All 14 conserved core subunits and
31 mitochondria-specific supernumerary subunits are resolved within the L-shaped
molecule. The hydrophilic matrix arm comprises flavin mononucleotide and 8 iron-sulfur
clusters involved in electron transfer, and the membrane arm contains 78 transmembrane
helices, mostly contributed by antiporter-like subunits involved in proton translocation.
Supernumerary subunits form an interlinked, stabilizing shell around the conserved
core. Tightly bound lipids (including cardiolipins) further stabilize interactions
between the hydrophobic subunits. Subunits with possible regulatory roles contain
additional cofactors, NADPH and two phosphopantetheine molecules, which are shown
to be involved in inter-subunit interactions. We observe two different conformations
of the complex, which may be related to the conformationally driven coupling mechanism
and to the active-deactive transition of the enzyme. Our structure provides insight
into the mechanism, assembly, maturation and dysfunction of mitochondrial complex
I, and allows detailed molecular analysis of disease-causing mutations.
article_processing_charge: No
article_type: original
author:
- first_name: Karol
full_name: Fiedorczuk, Karol
id: 5BFF67CE-02D1-11E9-B11A-A5A4D7DFFFD0
last_name: Fiedorczuk
- first_name: James A
full_name: Letts, James A
id: 322DA418-F248-11E8-B48F-1D18A9856A87
last_name: Letts
orcid: 0000-0002-9864-3586
- first_name: Gianluca
full_name: Degliesposti, Gianluca
last_name: Degliesposti
- first_name: Karol
full_name: Kaszuba, Karol
id: 3FDF9472-F248-11E8-B48F-1D18A9856A87
last_name: Kaszuba
- first_name: Mark
full_name: Skehel, Mark
last_name: Skehel
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
citation:
ama: Fiedorczuk K, Letts JA, Degliesposti G, Kaszuba K, Skehel M, Sazanov LA. Atomic
structure of the entire mammalian mitochondrial complex i. Nature. 2016;538(7625):406-410.
doi:10.1038/nature19794
apa: Fiedorczuk, K., Letts, J. A., Degliesposti, G., Kaszuba, K., Skehel, M., &
Sazanov, L. A. (2016). Atomic structure of the entire mammalian mitochondrial
complex i. Nature. Nature Publishing Group. https://doi.org/10.1038/nature19794
chicago: Fiedorczuk, Karol, James A Letts, Gianluca Degliesposti, Karol Kaszuba,
Mark Skehel, and Leonid A Sazanov. “Atomic Structure of the Entire Mammalian Mitochondrial
Complex I.” Nature. Nature Publishing Group, 2016. https://doi.org/10.1038/nature19794.
ieee: K. Fiedorczuk, J. A. Letts, G. Degliesposti, K. Kaszuba, M. Skehel, and L.
A. Sazanov, “Atomic structure of the entire mammalian mitochondrial complex i,”
Nature, vol. 538, no. 7625. Nature Publishing Group, pp. 406–410, 2016.
ista: Fiedorczuk K, Letts JA, Degliesposti G, Kaszuba K, Skehel M, Sazanov LA. 2016.
Atomic structure of the entire mammalian mitochondrial complex i. Nature. 538(7625),
406–410.
mla: Fiedorczuk, Karol, et al. “Atomic Structure of the Entire Mammalian Mitochondrial
Complex I.” Nature, vol. 538, no. 7625, Nature Publishing Group, 2016,
pp. 406–10, doi:10.1038/nature19794.
short: K. Fiedorczuk, J.A. Letts, G. Degliesposti, K. Kaszuba, M. Skehel, L.A. Sazanov,
Nature 538 (2016) 406–410.
date_created: 2018-12-11T11:50:49Z
date_published: 2016-10-20T00:00:00Z
date_updated: 2021-01-12T06:49:13Z
day: '20'
department:
- _id: LeSa
doi: 10.1038/nature19794
ec_funded: 1
external_id:
pmid:
- '27595392'
intvolume: ' 538'
issue: '7625'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5164932/
month: '10'
oa: 1
oa_version: Submitted Version
page: 406 - 410
pmid: 1
project:
- _id: 2593EBD6-B435-11E9-9278-68D0E5697425
name: Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes
(FEBS)
- _id: 2590DB08-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '701309'
name: Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes
(H2020)
publication: Nature
publication_status: published
publisher: Nature Publishing Group
publist_id: '6108'
quality_controlled: '1'
scopus_import: 1
status: public
title: Atomic structure of the entire mammalian mitochondrial complex i
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 538
year: '2016'
...