In-cell architecture of the mitochondrial respiratory chain

Science. 2025 Mar 21;387(6740):1296-1301. doi: 10.1126/science.ads8738. Epub 2025 Mar 20.

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.

MeSH terms

  • Adenosine Triphosphate* / biosynthesis
  • Chlamydomonas reinhardtii* / enzymology
  • Chlamydomonas reinhardtii* / metabolism
  • Chlamydomonas reinhardtii* / ultrastructure
  • Cryoelectron Microscopy
  • Cytochromes c / chemistry
  • Electron Microscope Tomography
  • Electron Transport
  • Electron Transport Complex I / chemistry
  • Electron Transport Complex I / ultrastructure
  • Electron Transport Complex III / chemistry
  • Electron Transport Complex III / ultrastructure
  • Electron Transport Complex IV / chemistry
  • Electron Transport Complex IV / ultrastructure
  • Mitochondria* / enzymology
  • Mitochondria* / ultrastructure
  • Mitochondrial Membranes / ultrastructure
  • Oxidative Phosphorylation
  • Protein Domains

Substances

  • Adenosine Triphosphate
  • Cytochromes c
  • Electron Transport Complex I
  • Electron Transport Complex III
  • Electron Transport Complex IV