bims-resufa Biomed News
on Respiratory supercomplex factors
Issue of 2019‒06‒16
two papers selected by
Vera Strogolova
Marquette University

  1. Comput Struct Biotechnol J. 2019 ;17 654-660
    Pérez-Mejías G, Guerra-Castellano A, Díaz-Quintana A, De la Rosa MA, Díaz-Moreno I.
      The proper arrangement of protein components within the respiratory electron transport chain is nowadays a matter of intense debate, since altering it leads to cell aging and other related pathologies. Here, we discuss three current views-the so-called solid, fluid and plasticity models-which describe the organization of the main membrane-embedded mitochondrial protein complexes and the key elements that regulate and/or facilitate supercomplex assembly. The soluble electron carrier cytochrome c has recently emerged as an essential factor in the assembly and function of respiratory supercomplexes. In fact, a 'restricted diffusion pathway' mechanism for electron transfer between complexes III and IV has been proposed based on the secondary, distal binding sites for cytochrome c at its two membrane partners recently discovered. This channeling pathway facilitates the surfing of cytochrome c on both respiratory complexes, thereby tuning the efficiency of oxidative phosphorylation and diminishing the production of reactive oxygen species. The well-documented post-translational modifications of cytochrome c could further contribute to the rapid adjustment of electron flow in response to changing cellular conditions.
    Keywords:  Cytochrome c; Mitochondria; Phosphorylation; Reactive oxygen species; Respiratory supercomplexes
  2. Antimicrob Agents Chemother. 2019 Jun 10. pii: AAC.00374-19. [Epub ahead of print]
    Yamashita K, Miyazaki T, Fukuda Y, Mitsuyama J, Saijo T, Shimamura S, Yamamoto K, Imamura Y, Izumikawa K, Yanagihara K, Kohno S, Mukae H.
      The novel arylamidine T-2307 exhibits broad-spectrum in vitro and in vivo antifungal activities against clinically significant pathogens. Previous studies have shown that T-2307 accumulates in yeast cells via a specific polyamine transporter and disrupts yeast mitochondrial membrane potential. Further, it has little effect on rat liver mitochondrial function. The mechanism by which T-2307 disrupts yeast mitochondrial function is poorly understood, and its elucidation may provide important information for developing novel antifungal agents. This study aimed to understand how T-2307 promotes yeast mitochondrial dysfunction and to investigate the selectivity of this mechanism between fungi and mammals. T-2307 inhibited the respiration of yeast whole cells and isolated yeast mitochondria in a dose-dependent manner. The similarity of the effects of T-2307 and respiratory chain inhibitors on mitochondrial respiration prompted us to investigate the effect of T-2307 on mitochondrial respiratory chain complexes. T-2307 particularly inhibited respiratory chain complexes III and IV not only in Saccharomyces cerevisiae but also in Candida albicans, indicating that T-2307 acts against pathogenic fungi in a manner similar to that of yeast. Conversely, T-2307 showed little effect on bovine respiratory chain complexes. Additionally, we demonstrated that the inhibition of respiratory chain complexes by T-2307 resulted in a decrease in the intracellular ATP levels in yeast cells. These results indicate that the inhibition of respiratory chain complexes III and IV is a key for selective disruption of yeast mitochondrial function and antifungal activity.