In-cell architecture of the mitochondrial respiratory chain

• 成果类型: Article
• 署名作者: Waltz, Florent; Righetto, Ricardo D.; Lamm, Lorenz; Salinas-Giege, Thalia; Kelley, Ron; Zhang, Xianjun; Obr, Martin; Khavnekar, Sagar; Kotecha, Abhay; Engel, Benjamin D.
• 署名单位: University of Basel; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Centre National de la Recherche Scientifique (CNRS); Thermo Fisher Scientific; Max Planck Society; St Jude Children's Research Hospital
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9740
• DOI: 10.1126/science.ads8738
• 发表日期: 2025-03-21
• 页码: 1296-1301
• 关键词: cytochrome-c-oxidase; complex-i; electron-microscopy; coupling mechanism; atp synthase; situ; supercomplex; phosphorylation; Visualization; ORGANIZATION

摘要

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 (angstrom) resolution structure showing binding of electron carrier cytochrome c. Combined with single-particle cryo-electron microscopy at 2.4-angstrom resolution, we model how the respiratory complexes organize inside native mitochondria.