---
_id: '7395'
abstract:
- lang: eng
  text: The mitochondrial electron transport chain complexes are organized into supercomplexes
    (SCs) of defined stoichiometry, which have been proposed to regulate electron
    flux via substrate channeling. We demonstrate that CoQ trapping in the isolated
    SC I+III2 limits complex (C)I turnover, arguing against channeling. The SC structure,
    resolved at up to 3.8 Å in four distinct states, suggests that CoQ oxidation may
    be rate limiting because of unequal access of CoQ to the active sites of CIII2.
    CI shows a transition between “closed” and “open” conformations, accompanied by
    the striking rotation of a key transmembrane helix. Furthermore, the state of
    CI affects the conformational flexibility within CIII2, demonstrating crosstalk
    between the enzymes. CoQ was identified at only three of the four binding sites
    in CIII2, suggesting that interaction with CI disrupts CIII2 symmetry in a functionally
    relevant manner. Together, these observations indicate a more nuanced functional
    role for the SCs.
article_processing_charge: No
article_type: original
author:
- 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: Karol
  full_name: Fiedorczuk, Karol
  id: 5BFF67CE-02D1-11E9-B11A-A5A4D7DFFFD0
  last_name: Fiedorczuk
- first_name: Gianluca
  full_name: Degliesposti, Gianluca
  last_name: Degliesposti
- 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: Letts JA, Fiedorczuk K, Degliesposti G, Skehel M, Sazanov LA. Structures of
    respiratory supercomplex I+III2 reveal functional and conformational crosstalk.
    <i>Molecular Cell</i>. 2019;75(6):1131-1146.e6. doi:<a href="https://doi.org/10.1016/j.molcel.2019.07.022">10.1016/j.molcel.2019.07.022</a>
  apa: Letts, J. A., Fiedorczuk, K., Degliesposti, G., Skehel, M., &#38; Sazanov,
    L. A. (2019). Structures of respiratory supercomplex I+III2 reveal functional
    and conformational crosstalk. <i>Molecular Cell</i>. Cell Press. <a href="https://doi.org/10.1016/j.molcel.2019.07.022">https://doi.org/10.1016/j.molcel.2019.07.022</a>
  chicago: Letts, James A, Karol Fiedorczuk, Gianluca Degliesposti, Mark Skehel, and
    Leonid A Sazanov. “Structures of Respiratory Supercomplex I+III2 Reveal Functional
    and Conformational Crosstalk.” <i>Molecular Cell</i>. Cell Press, 2019. <a href="https://doi.org/10.1016/j.molcel.2019.07.022">https://doi.org/10.1016/j.molcel.2019.07.022</a>.
  ieee: J. A. Letts, K. Fiedorczuk, G. Degliesposti, M. Skehel, and L. A. Sazanov,
    “Structures of respiratory supercomplex I+III2 reveal functional and conformational
    crosstalk,” <i>Molecular Cell</i>, vol. 75, no. 6. Cell Press, p. 1131–1146.e6,
    2019.
  ista: Letts JA, Fiedorczuk K, Degliesposti G, Skehel M, Sazanov LA. 2019. Structures
    of respiratory supercomplex I+III2 reveal functional and conformational crosstalk.
    Molecular Cell. 75(6), 1131–1146.e6.
  mla: Letts, James A., et al. “Structures of Respiratory Supercomplex I+III2 Reveal
    Functional and Conformational Crosstalk.” <i>Molecular Cell</i>, vol. 75, no.
    6, Cell Press, 2019, p. 1131–1146.e6, doi:<a href="https://doi.org/10.1016/j.molcel.2019.07.022">10.1016/j.molcel.2019.07.022</a>.
  short: J.A. Letts, K. Fiedorczuk, G. Degliesposti, M. Skehel, L.A. Sazanov, Molecular
    Cell 75 (2019) 1131–1146.e6.
corr_author: '1'
date_created: 2020-01-29T16:02:33Z
date_published: 2019-09-19T00:00:00Z
date_updated: 2024-10-22T09:34:12Z
day: '19'
ddc:
- '570'
department:
- _id: LeSa
doi: 10.1016/j.molcel.2019.07.022
ec_funded: 1
external_id:
  isi:
  - '000486614200006'
  pmid:
  - '31492636'
file:
- access_level: open_access
  checksum: 5202f53a237d6650ece038fbf13bdcea
  content_type: application/pdf
  creator: dernst
  date_created: 2020-02-04T10:37:28Z
  date_updated: 2020-07-14T12:47:57Z
  file_id: '7447'
  file_name: 2019_MolecularCell_Letts.pdf
  file_size: 9654895
  relation: main_file
file_date_updated: 2020-07-14T12:47:57Z
has_accepted_license: '1'
intvolume: '        75'
isi: 1
issue: '6'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: 1131-1146.e6
pmid: 1
project:
- _id: 2590DB08-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '701309'
  name: Atomic Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes
publication: Molecular Cell
publication_identifier:
  issn:
  - 1097-2765
publication_status: published
publisher: Cell Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Structures of respiratory supercomplex I+III2 reveal functional and conformational
  crosstalk
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 75
year: '2019'
...
---
_id: '466'
abstract:
- lang: eng
  text: 'We consider Markov decision processes (MDPs) with multiple limit-average
    (or mean-payoff) objectives. There exist two different views: (i) the expectation
    semantics, where the goal is to optimize the expected mean-payoff objective, and
    (ii) the satisfaction semantics, where the goal is to maximize the probability
    of runs such that the mean-payoff value stays above a given vector. We consider
    optimization with respect to both objectives at once, thus unifying the existing
    semantics. Precisely, the goal is to optimize the expectation while ensuring the
    satisfaction constraint. Our problem captures the notion of optimization with
    respect to strategies that are risk-averse (i.e., ensure certain probabilistic
    guarantee). Our main results are as follows: First, we present algorithms for
    the decision problems which are always polynomial in the size of the MDP. We also
    show that an approximation of the Pareto-curve can be computed in time polynomial
    in the size of the MDP, and the approximation factor, but exponential in the number
    of dimensions. Second, we present a complete characterization of the strategy
    complexity (in terms of memory bounds and randomization) required to solve our
    problem. '
article_number: '15'
article_processing_charge: No
author:
- first_name: Krishnendu
  full_name: Chatterjee, Krishnendu
  id: 2E5DCA20-F248-11E8-B48F-1D18A9856A87
  last_name: Chatterjee
  orcid: 0000-0002-4561-241X
- first_name: Zuzana
  full_name: Křetínská, Zuzana
  last_name: Křetínská
- first_name: Jan
  full_name: Kretinsky, Jan
  id: 44CEF464-F248-11E8-B48F-1D18A9856A87
  last_name: Kretinsky
  orcid: 0000-0002-8122-2881
citation:
  ama: Chatterjee K, Křetínská Z, Kretinsky J. Unifying two views on multiple mean-payoff
    objectives in Markov decision processes. <i>Logical Methods in Computer Science</i>.
    2017;13(2). doi:<a href="https://doi.org/10.23638/LMCS-13(2:15)2017">10.23638/LMCS-13(2:15)2017</a>
  apa: Chatterjee, K., Křetínská, Z., &#38; Kretinsky, J. (2017). Unifying two views
    on multiple mean-payoff objectives in Markov decision processes. <i>Logical Methods
    in Computer Science</i>. International Federation of Computational Logic. <a href="https://doi.org/10.23638/LMCS-13(2:15)2017">https://doi.org/10.23638/LMCS-13(2:15)2017</a>
  chicago: Chatterjee, Krishnendu, Zuzana Křetínská, and Jan Kretinsky. “Unifying
    Two Views on Multiple Mean-Payoff Objectives in Markov Decision Processes.” <i>Logical
    Methods in Computer Science</i>. International Federation of Computational Logic,
    2017. <a href="https://doi.org/10.23638/LMCS-13(2:15)2017">https://doi.org/10.23638/LMCS-13(2:15)2017</a>.
  ieee: K. Chatterjee, Z. Křetínská, and J. Kretinsky, “Unifying two views on multiple
    mean-payoff objectives in Markov decision processes,” <i>Logical Methods in Computer
    Science</i>, vol. 13, no. 2. International Federation of Computational Logic,
    2017.
  ista: Chatterjee K, Křetínská Z, Kretinsky J. 2017. Unifying two views on multiple
    mean-payoff objectives in Markov decision processes. Logical Methods in Computer
    Science. 13(2), 15.
  mla: Chatterjee, Krishnendu, et al. “Unifying Two Views on Multiple Mean-Payoff
    Objectives in Markov Decision Processes.” <i>Logical Methods in Computer Science</i>,
    vol. 13, no. 2, 15, International Federation of Computational Logic, 2017, doi:<a
    href="https://doi.org/10.23638/LMCS-13(2:15)2017">10.23638/LMCS-13(2:15)2017</a>.
  short: K. Chatterjee, Z. Křetínská, J. Kretinsky, Logical Methods in Computer Science
    13 (2017).
corr_author: '1'
date_created: 2018-12-11T11:46:38Z
date_published: 2017-07-03T00:00:00Z
date_updated: 2025-09-29T11:00:42Z
day: '03'
ddc:
- '004'
department:
- _id: KrCh
doi: 10.23638/LMCS-13(2:15)2017
ec_funded: 1
external_id:
  isi:
  - '000419160800002'
file:
- access_level: open_access
  checksum: bfa405385ec6229ad5ead89ab5751639
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:18:32Z
  date_updated: 2020-07-14T12:46:33Z
  file_id: '5354'
  file_name: IST-2018-957-v1+1_2017_Chatterjee_Unifying_two.pdf
  file_size: 511832
  relation: main_file
file_date_updated: 2020-07-14T12:46:33Z
has_accepted_license: '1'
intvolume: '        13'
isi: 1
issue: '2'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nd/4.0/
month: '07'
oa: 1
oa_version: Published Version
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
- _id: 2584A770-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P 23499-N23
  name: Modern Graph Algorithmic Techniques in Formal Verification
- _id: 2581B60A-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '279307'
  name: 'Quantitative Graph Games: Theory and Applications'
- _id: 2590DB08-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '701309'
  name: Atomic Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes
publication: Logical Methods in Computer Science
publication_identifier:
  issn:
  - 1860-5974
publication_status: published
publisher: International Federation of Computational Logic
publist_id: '7355'
pubrep_id: '957'
quality_controlled: '1'
related_material:
  record:
  - id: '5429'
    relation: earlier_version
    status: public
  - id: '5435'
    relation: earlier_version
    status: public
  - id: '1657'
    relation: earlier_version
    status: public
scopus_import: '1'
status: public
title: Unifying two views on multiple mean-payoff objectives in Markov decision processes
tmp:
  image: /image/cc_by_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nd/4.0/legalcode
  name: Creative Commons Attribution-NoDerivatives 4.0 International (CC BY-ND 4.0)
  short: CC BY-ND (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 13
year: '2017'
...
---
_id: '515'
abstract:
- lang: eng
  text: 'The oxidative phosphorylation electron transport chain (OXPHOS-ETC) of the
    inner mitochondrial membrane is composed of five large protein complexes, named
    CI-CV. These complexes convert energy from the food we eat into ATP, a small molecule
    used to power a multitude of essential reactions throughout the cell. OXPHOS-ETC
    complexes are organized into supercomplexes (SCs) of defined stoichiometry: CI
    forms a supercomplex with CIII2 and CIV (SC I+III2+IV, known as the respirasome),
    as well as with CIII2 alone (SC I+III2). CIII2 forms a supercomplex with CIV (SC
    III2+IV) and CV forms dimers (CV2). Recent cryo-EM studies have revealed the structures
    of SC I+III2+IV and SC I+III2. Furthermore, recent work has shed light on the
    assembly and function of the SCs. Here we review and compare these recent studies
    and discuss how they have advanced our understanding of mitochondrial electron
    transport.'
article_processing_charge: No
article_type: original
author:
- 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: Leonid A
  full_name: Sazanov, Leonid A
  id: 338D39FE-F248-11E8-B48F-1D18A9856A87
  last_name: Sazanov
  orcid: 0000-0002-0977-7989
citation:
  ama: 'Letts JA, Sazanov LA. Clarifying the supercomplex: The higher-order organization
    of the mitochondrial electron transport chain. <i>Nature Structural and Molecular
    Biology</i>. 2017;24(10):800-808. doi:<a href="https://doi.org/10.1038/nsmb.3460">10.1038/nsmb.3460</a>'
  apa: 'Letts, J. A., &#38; Sazanov, L. A. (2017). Clarifying the supercomplex: The
    higher-order organization of the mitochondrial electron transport chain. <i>Nature
    Structural and Molecular Biology</i>. Nature Publishing Group. <a href="https://doi.org/10.1038/nsmb.3460">https://doi.org/10.1038/nsmb.3460</a>'
  chicago: 'Letts, James A, and Leonid A Sazanov. “Clarifying the Supercomplex: The
    Higher-Order Organization of the Mitochondrial Electron Transport Chain.” <i>Nature
    Structural and Molecular Biology</i>. Nature Publishing Group, 2017. <a href="https://doi.org/10.1038/nsmb.3460">https://doi.org/10.1038/nsmb.3460</a>.'
  ieee: 'J. A. Letts and L. A. Sazanov, “Clarifying the supercomplex: The higher-order
    organization of the mitochondrial electron transport chain,” <i>Nature Structural
    and Molecular Biology</i>, vol. 24, no. 10. Nature Publishing Group, pp. 800–808,
    2017.'
  ista: 'Letts JA, Sazanov LA. 2017. Clarifying the supercomplex: The higher-order
    organization of the mitochondrial electron transport chain. Nature Structural
    and Molecular Biology. 24(10), 800–808.'
  mla: 'Letts, James A., and Leonid A. Sazanov. “Clarifying the Supercomplex: The
    Higher-Order Organization of the Mitochondrial Electron Transport Chain.” <i>Nature
    Structural and Molecular Biology</i>, vol. 24, no. 10, Nature Publishing Group,
    2017, pp. 800–08, doi:<a href="https://doi.org/10.1038/nsmb.3460">10.1038/nsmb.3460</a>.'
  short: J.A. Letts, L.A. Sazanov, Nature Structural and Molecular Biology 24 (2017)
    800–808.
corr_author: '1'
date_created: 2018-12-11T11:46:54Z
date_published: 2017-10-05T00:00:00Z
date_updated: 2025-09-18T09:47:41Z
day: '05'
ddc:
- '572'
department:
- _id: LeSa
doi: 10.1038/nsmb.3460
ec_funded: 1
external_id:
  isi:
  - '000412278000006'
file:
- access_level: open_access
  checksum: 9bc7e8c41b43636dd7566289e511f096
  content_type: application/pdf
  creator: lsazanov
  date_created: 2019-11-07T12:51:07Z
  date_updated: 2020-07-14T12:46:36Z
  file_id: '6993'
  file_name: 29893_2_merged_1501257589_red.pdf
  file_size: 4118385
  relation: main_file
file_date_updated: 2020-07-14T12:46:36Z
has_accepted_license: '1'
intvolume: '        24'
isi: 1
issue: '10'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Submitted Version
page: 800 - 808
project:
- _id: 2590DB08-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '701309'
  name: Atomic Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes
publication: Nature Structural and Molecular Biology
publication_identifier:
  issn:
  - 1545-9993
publication_status: published
publisher: Nature Publishing Group
publist_id: '7304'
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Clarifying the supercomplex: The higher-order organization of the mitochondrial
  electron transport chain'
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 24
year: '2017'
...
---
_id: '568'
abstract:
- lang: eng
  text: 'We study robust properties of zero sets of continuous maps f: X → ℝn. Formally,
    we analyze the family Z&lt; r(f) := (g-1(0): ||g - f|| &lt; r) of all zero sets
    of all continuous maps g closer to f than r in the max-norm. All of these sets
    are outside A := (x: |f(x)| ≥ r) and we claim that Z&lt; r(f) is fully determined
    by A and an element of a certain cohomotopy group which (by a recent result) is
    computable whenever the dimension of X is at most 2n - 3. By considering all r
    &gt; 0 simultaneously, the pointed cohomotopy groups form a persistence module-a
    structure leading to persistence diagrams as in the case of persistent homology
    or well groups. Eventually, we get a descriptor of persistent robust properties
    of zero sets that has better descriptive power (Theorem A) and better computability
    status (Theorem B) than the established well diagrams. Moreover, if we endow every
    point of each zero set with gradients of the perturbation, the robust description
    of the zero sets by elements of cohomotopy groups is in some sense the best possible
    (Theorem C).'
article_processing_charge: No
arxiv: 1
author:
- first_name: Peter
  full_name: Franek, Peter
  id: 473294AE-F248-11E8-B48F-1D18A9856A87
  last_name: Franek
  orcid: 0000-0001-8878-8397
- first_name: Marek
  full_name: Krcál, Marek
  id: 33E21118-F248-11E8-B48F-1D18A9856A87
  last_name: Krcál
citation:
  ama: Franek P, Krcál M. Persistence of zero sets. <i>Homology, Homotopy and Applications</i>.
    2017;19(2):313-342. doi:<a href="https://doi.org/10.4310/HHA.2017.v19.n2.a16">10.4310/HHA.2017.v19.n2.a16</a>
  apa: Franek, P., &#38; Krcál, M. (2017). Persistence of zero sets. <i>Homology,
    Homotopy and Applications</i>. International Press. <a href="https://doi.org/10.4310/HHA.2017.v19.n2.a16">https://doi.org/10.4310/HHA.2017.v19.n2.a16</a>
  chicago: Franek, Peter, and Marek Krcál. “Persistence of Zero Sets.” <i>Homology,
    Homotopy and Applications</i>. International Press, 2017. <a href="https://doi.org/10.4310/HHA.2017.v19.n2.a16">https://doi.org/10.4310/HHA.2017.v19.n2.a16</a>.
  ieee: P. Franek and M. Krcál, “Persistence of zero sets,” <i>Homology, Homotopy
    and Applications</i>, vol. 19, no. 2. International Press, pp. 313–342, 2017.
  ista: Franek P, Krcál M. 2017. Persistence of zero sets. Homology, Homotopy and
    Applications. 19(2), 313–342.
  mla: Franek, Peter, and Marek Krcál. “Persistence of Zero Sets.” <i>Homology, Homotopy
    and Applications</i>, vol. 19, no. 2, International Press, 2017, pp. 313–42, doi:<a
    href="https://doi.org/10.4310/HHA.2017.v19.n2.a16">10.4310/HHA.2017.v19.n2.a16</a>.
  short: P. Franek, M. Krcál, Homology, Homotopy and Applications 19 (2017) 313–342.
corr_author: '1'
date_created: 2018-12-11T11:47:14Z
date_published: 2017-01-01T00:00:00Z
date_updated: 2025-09-11T07:41:51Z
day: '01'
department:
- _id: UlWa
- _id: HeEd
doi: 10.4310/HHA.2017.v19.n2.a16
ec_funded: 1
external_id:
  arxiv:
  - '1507.04310'
  isi:
  - '000440749400010'
intvolume: '        19'
isi: 1
issue: '2'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://arxiv.org/abs/1507.04310
month: '01'
oa: 1
oa_version: Submitted Version
page: 313 - 342
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
- _id: 2590DB08-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '701309'
  name: Atomic Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes
publication: Homology, Homotopy and Applications
publication_identifier:
  issn:
  - 1532-0073
publication_status: published
publisher: International Press
publist_id: '7246'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Persistence of zero sets
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 19
year: '2017'
...
---
_id: '1209'
abstract:
- lang: eng
  text: 'NADH-ubiquinone oxidoreductase (complex I) is the largest (∼1 MDa) and the
    least characterized complex of the mitochondrial electron transport chain. Because
    of the ease of sample availability, previous work has focused almost exclusively
    on bovine complex I. However, only medium resolution structural analyses of this
    complex have been reported. Working with other mammalian complex I homologues
    is a potential approach for overcoming these limitations. Due to the inherent
    difficulty of expressing large membrane protein complexes, screening of complex
    I homologues is limited to large mammals reared for human consumption. The high
    sequence identity among these available sources may preclude the benefits of screening.
    Here, we report the characterization of complex I purified from Ovis aries (ovine)
    heart mitochondria. All 44 unique subunits of the intact complex were identified
    by mass spectrometry. We identified differences in the subunit composition of
    subcomplexes of ovine complex I as compared with bovine, suggesting differential
    stability of inter-subunit interactions within the complex. Furthermore, the 42-kDa
    subunit, which is easily lost from the bovine enzyme, remains tightly bound to
    ovine complex I. Additionally, we developed a novel purification protocol for
    highly active and stable mitochondrial complex I using the branched-chain detergent
    lauryl maltose neopentyl glycol. Our data demonstrate that, although closely related,
    significant differences exist between the biochemical properties of complex I
    prepared from ovine and bovine mitochondria and that ovine complex I represents
    a suitable alternative target for further structural studies. '
acknowledgement: "J.A.S supported in part by a Medical Research D.G.Council UK Ph.D.
  fellowship.\r\nThis work was supported in part by European Union's 2020 Research
  and Innovation Program under Grant 701309. \r\n"
article_processing_charge: No
author:
- 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: Fiedorczuk, Karol
  id: 5BFF67CE-02D1-11E9-B11A-A5A4D7DFFFD0
  last_name: Fiedorczuk
- 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: Letts JA, Degliesposti G, Fiedorczuk K, Skehel M, Sazanov LA. Purification
    of ovine respiratory complex i results in a highly active and stable preparation.
    <i>Journal of Biological Chemistry</i>. 2016;291(47):24657-24675. doi:<a href="https://doi.org/10.1074/jbc.M116.735142">10.1074/jbc.M116.735142</a>
  apa: Letts, J. A., Degliesposti, G., Fiedorczuk, K., Skehel, M., &#38; Sazanov,
    L. A. (2016). Purification of ovine respiratory complex i results in a highly
    active and stable preparation. <i>Journal of Biological Chemistry</i>. American
    Society for Biochemistry and Molecular Biology. <a href="https://doi.org/10.1074/jbc.M116.735142">https://doi.org/10.1074/jbc.M116.735142</a>
  chicago: Letts, James A, Gianluca Degliesposti, Karol Fiedorczuk, Mark Skehel, and
    Leonid A Sazanov. “Purification of Ovine Respiratory Complex i Results in a Highly
    Active and Stable Preparation.” <i>Journal of Biological Chemistry</i>. American
    Society for Biochemistry and Molecular Biology, 2016. <a href="https://doi.org/10.1074/jbc.M116.735142">https://doi.org/10.1074/jbc.M116.735142</a>.
  ieee: J. A. Letts, G. Degliesposti, K. Fiedorczuk, M. Skehel, and L. A. Sazanov,
    “Purification of ovine respiratory complex i results in a highly active and stable
    preparation,” <i>Journal of Biological Chemistry</i>, vol. 291, no. 47. American
    Society for Biochemistry and Molecular Biology, pp. 24657–24675, 2016.
  ista: Letts JA, Degliesposti G, Fiedorczuk K, Skehel M, Sazanov LA. 2016. Purification
    of ovine respiratory complex i results in a highly active and stable preparation.
    Journal of Biological Chemistry. 291(47), 24657–24675.
  mla: Letts, James A., et al. “Purification of Ovine Respiratory Complex i Results
    in a Highly Active and Stable Preparation.” <i>Journal of Biological Chemistry</i>,
    vol. 291, no. 47, American Society for Biochemistry and Molecular Biology, 2016,
    pp. 24657–75, doi:<a href="https://doi.org/10.1074/jbc.M116.735142">10.1074/jbc.M116.735142</a>.
  short: J.A. Letts, G. Degliesposti, K. Fiedorczuk, M. Skehel, L.A. Sazanov, Journal
    of Biological Chemistry 291 (2016) 24657–24675.
corr_author: '1'
date_created: 2018-12-11T11:50:44Z
date_published: 2016-11-18T00:00:00Z
date_updated: 2025-09-22T09:38:04Z
day: '18'
department:
- _id: LeSa
doi: 10.1074/jbc.M116.735142
ec_funded: 1
external_id:
  isi:
  - '000388875500026'
intvolume: '       291'
isi: 1
issue: '47'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114416/
month: '11'
oa: 1
oa_version: Submitted Version
page: 24657 - 24675
project:
- _id: 2593EBD6-B435-11E9-9278-68D0E5697425
  name: Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes
- _id: 2590DB08-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '701309'
  name: Atomic Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes
publication: Journal of Biological Chemistry
publication_status: published
publisher: American Society for Biochemistry and Molecular Biology
publist_id: '6139'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Purification of ovine respiratory complex i results in a highly active and
  stable preparation
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 291
year: '2016'
...
---
_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. <i>Nature</i>. 2016;538(7625):406-410.
    doi:<a href="https://doi.org/10.1038/nature19794">10.1038/nature19794</a>
  apa: Fiedorczuk, K., Letts, J. A., Degliesposti, G., Kaszuba, K., Skehel, M., &#38;
    Sazanov, L. A. (2016). Atomic structure of the entire mammalian mitochondrial
    complex i. <i>Nature</i>. Nature Publishing Group. <a href="https://doi.org/10.1038/nature19794">https://doi.org/10.1038/nature19794</a>
  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.” <i>Nature</i>. Nature Publishing Group, 2016. <a href="https://doi.org/10.1038/nature19794">https://doi.org/10.1038/nature19794</a>.
  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,”
    <i>Nature</i>, 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.” <i>Nature</i>, vol. 538, no. 7625, Nature Publishing Group, 2016,
    pp. 406–10, doi:<a href="https://doi.org/10.1038/nature19794">10.1038/nature19794</a>.
  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: 2025-09-22T09:29:26Z
day: '20'
department:
- _id: LeSa
doi: 10.1038/nature19794
ec_funded: 1
external_id:
  isi:
  - '000386673100044'
  pmid:
  - '27595392'
intvolume: '       538'
isi: 1
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
- _id: 2590DB08-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '701309'
  name: Atomic Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 538
year: '2016'
...