bims-resufa Biomed News
on Respiratory supercomplex factors
Issue of 2025–03–16
two papers selected by
Gavin McStay, Liverpool John Moores University
  1. Visualizing mitochondrial electron transport chain complexes and super-complexes during infection of human macrophages with Legionella pneumophila.
  2. The flexible chain: regulation of structure and activity of ETC complexes defines rate of ATP synthesis and sites of superoxide generation.
  1. Methods Cell Biol. 2025 ;pii: S0091-679X(24)00016-5. [Epub ahead of print]194 19-42
    Visualizing mitochondrial electron transport chain complexes and super-complexes during infection of human macrophages with Legionella pneumophila.
    Mariatou Dramé, Daniel Schator, Carmen Buchrieser, Pedro Escoll.
      The ultrastructure of mitochondria is pivotal for their respiratory activity. Thus, the regulation of the assembly of the super-complexes (SCs) of the mitochondrial electron transport chain (ETC) might be a core aspect of macrophage immunometabolism during bacterial infection. In order to study the impact of infection by Legionella pneumophila on the configuration of mitochondrial complexes and SCs in human macrophages, we have adapted and combined different methods such as cell sorting of infected cells, magnetic isolation of highly pure and functional mitochondria, quality control of mitochondrial purity by flow cytometry, and BN-PAGE (Blue-Native Polyacrylamide Gel Electrophoresis) coupled to Western Blot using near-infrared (NIR) fluorescence. The here presented protocol uses infected and non-infected human macrophage-like THP-1 cells and GFP-expressing L. pneumophila, but the method can be used to analyze the configuration of ETC complexes and SCs also in other mammalian cells and infected with different intracellular bacteria expressing a fluorescent protein.
    Keywords:  Blue-native PAGE; Electron transport chain; Human macrophages; Legionella pneumophila; Mitochondria; Mitochondria isolation; OXPHOS; Super-complexes; THP-1
    DOI:  https://doi.org/10.1016/bs.mcb.2024.01.003
  2. Biophys Rev. 2025 Feb;17(1): 55-88
    The flexible chain: regulation of structure and activity of ETC complexes defines rate of ATP synthesis and sites of superoxide generation.
    Zhanna V Bochkova, Adil A Baizhumanov, Alexander I Yusipovich, Kseniia I Morozova, Evelina I Nikelshparg, Anna A Fedotova, Alisa B Tiaglik, Yu Xu, Alexey R Brazhe, Georgy V Maksimov, Dmitry S Bilan, Yuliya V Khramova, Evgeniya Yu Parshina, Nadezda A Brazhe.
      This review highlights current insights into the regulation of the mitochondrial respiratory chain (electron transport chain, ETC) activity. The regulation of ETC properties optimizes ATP synthesis and controls the generation of the superoxide anion radical (O2 •-) which can be converted into other reactive oxygen species (ROS) playing a dual role by initiating signaling cascades or contributing to oxidative stress. We examine how ETC activity is influenced by the structure and conformation of its complexes, their allosteric or post-translational modifications, and their interactions with membrane lipids. The formation and function of supercomplexes, as well as their cell-type-specific characteristics, are also discussed, alongside with the role of intracellular Ca2+ concentration in the modulation of ETC activity. Furthermore, we discuss mechanisms and sites of O2 •- generation within ETC complexes, O2 •- fate in the mitochondrial matrix, and the impact of cytochrome c (Cyt c) conformation and allosteric modifications on ETC function. Finally, we discuss various abnormalities in ETC complexes, emphasizing their relevance to mitochondrial dysfunction and disease.
    Keywords:  Calcium ions; Electron transport; Electron transport chain; Mitochondria; Mitochondrial membranes; Reactive oxygen species
    DOI:  https://doi.org/10.1007/s12551-025-01270-5
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