Cited by 95Mitochondrial Function and PathologyAdvanced Electron Microscopy Techniques and ApplicationsATP Synthase and ATPases Research

In-cell architecture of the mitochondrial respiratory chain

Open access
Waltz, Florent, Righetto, Ricardo D., Lamm, Lorenz, Salinas-Giegé, Thalia, Kelley, Ron, Zhang, Xianjun, Obr, Martin, Khavnekar, Sagar +2 more·2025·Science

Published version of a preprint

Abstract

Mitochondria regenerate adenosine triphosphate (ATP) through oxidative phosphorylation. This process is carried out by five membrane-bound complexes collectively known as the respiratory chain, working in concert to transfer electrons and pump protons. The precise organization of these complexes in native cells is debated. We used in situ cryo–electron tomography to visualize the native structures and organization of several major mitochondrial complexes in Chlamydomonas reinhardtii cells. ATP synthases and respiratory complexes segregate into curved and flat crista membrane domains, respectively. Respiratory complexes I, III, and IV assemble into a respirasome supercomplex, from which we determined a native 5-angstrom (Å) resolution structure showing binding of electron carrier cytochrome c . Combined with single-particle cryo–electron microscopy at 2.4-Å resolution, we model how the respiratory complexes organize inside native mitochondria.

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Authors
Waltz, F., Righetto, R. D., Lamm, L., Salinas-Giegé, T., Kelley, R., Zhang, X., Obr, M., Khavnekar, S., Kotecha, A., & Engel, B. D.
Affiliations
  • University of Basel (CH)
  • Institut de biologie moléculaire des plantes, CNRS, Université de Strasbourg, Strasbourg, France.
  • Thermo Fisher Scientific (Netherlands) (NL)
  • St. Jude Children's Research Hospital (US)
Corresponding author
  • Waltz, Florent
  • Engel, Benjamin D.
Venue
Science
Published
2025-03-21
Volume
387
Issue
6740
Pages
1296-1301
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W4408704214
Cited by
95
References
4
Citations by year
2026: 59 · 2025: 34 · 2024: 2
FWCI
27.96
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Science (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
  • univOAK (4 institutions : Université de Strasbourg, Université de Haute Alsace, INSA Strasbourg, Bibliothèque Nationale et Universitaire de Strasbourg) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
Keywords
mitochondrial respiratory chain, respirasome, respiratory chain supercomplexes, mitochondrial complex I, mitochondrial complex III, mitochondrial complex IV, ATP synthase, cytochrome c binding, oxidative phosphorylation, Chlamydomonas reinhardtii, electron transfer
MeSH terms
Protein Domains, Adenosine Triphosphate, Electron Transport Complex IV, Electron Transport, Mitochondria, Oxidative Phosphorylation, Electron Transport Complex III, Chlamydomonas reinhardtii, Cryoelectron Microscopy, Mitochondrial Proton-Translocating ATPases, Electron Transport Complex I, Cytochromes c, Mitochondrial Membranes, Electron Microscope Tomography

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