bims-resufa Biomed News
on Respiratory supercomplex factors
Issue of 2023‒02‒19
two papers selected by
Vera Strogolova
Strong Microbials, Inc
  1. Cryo-EM structure and function of S. pombe complex IV with bound respiratory supercomplex factor.
  2. Mitochondrial respiration reduces exposure of the nucleus to oxygen.
  1. Commun Chem. 2023 Feb 16. 6(1): 32
    Cryo-EM structure and function of S. pombe complex IV with bound respiratory supercomplex factor.
    Agnes Moe, Pia Ädelroth, Peter Brzezinski, Linda Näsvik Öjemyr.
      Fission yeast Schizosaccharomyces pombe serves as model organism for studying higher eukaryotes. We combined the use of cryo-EM and spectroscopy to investigate the structure and function of affinity purified respiratory complex IV (CIV) from S. pombe. The reaction sequence of the reduced enzyme with O2 proceeds over a time scale of µs-ms, similar to that of the mammalian CIV. The cryo-EM structure of CIV revealed eleven subunits as well as a bound hypoxia-induced gene 1 (Hig1) domain of respiratory supercomplex factor 2 (Rcf2). These results suggest that binding of Rcf2 does not require the presence of a CIII-CIV supercomplex, i.e. Rcf2 is a component of CIV. An AlphaFold-Multimer model suggests that the Hig1 domains of both Rcf1 and Rcf2 bind at the same site of CIV suggesting that their binding is mutually exclusive. Furthermore, the differential functional effect of Rcf1 or Rcf2 is presumably caused by interactions of CIV with their different non-Hig1 domain parts.
    DOI:  https://doi.org/10.1038/s42004-023-00827-3
  2. J Biol Chem. 2023 Feb 14. pii: S0021-9258(23)00150-3. [Epub ahead of print] 103018
    Mitochondrial respiration reduces exposure of the nucleus to oxygen.
    Mateus Prates Mori, Rozhin Penjweini, Jin Ma, Greg Alspaugh, Alessio Andreoni, Young-Chae Kim, Ping-Yuan Wang, Jay R Knutson, Paul M Hwang.
      The endosymbiotic theory posits that ancient eukaryotic cells engulfed O2-consuming prokaryotes, which protected them against O2 toxicity. Previous studies have shown that cells lacking cytochrome c oxidase (COX), required for respiration, have increased DNA damage and reduced proliferation, which could be improved by reducing O2 exposure. With recently developed fluorescence lifetime microscopy (FLIM)-based probes demonstrating that the mitochondrial compartment has lower [O2] than the cytosol, we hypothesized that the perinuclear distribution of mitochondria in cells may create a barrier for O2 to access the nuclear core, potentially affecting cellular physiology and maintaining genomic integrity. To test this hypothesis, we utilized myoglobin (MB)-mCherry FLIM O2 sensors without subcellular targeting ("cytosol") or with targeting to the mitochondrion or nucleus for measuring their localized O2 homeostasis. Our results showed that, similar to the mitochondria, the nuclear [O2] was reduced by ∼20-40% compared to the cytosol under imposed O2 levels of ∼0.5-18.6%. Pharmacologic inhibition of respiration increased nuclear O2 levels, and reconstituting O2 consumption by COX reversed this increase. Similarly, genetic disruption of respiration by deleting SCO2, a gene essential for COX assembly, or restoring COX activity in SCO2-/- cells by transducing with SCO2 cDNA also replicated these changes in nuclear O2 levels. The results were further supported by the expression of genes known to be affected by cellular O2 availability. Our study reveals the potential for dynamic regulation of nuclear O2 levels by mitochondrial respiratory activity, which in turn could affect oxidative stress and cellular processes such as neurodegeneration and aging.
    Keywords:  Classification: Cell Biology; Metabolism; hypoxia; mitochondria; nucleus; oxygen; respiration
    DOI:  https://doi.org/10.1016/j.jbc.2023.103018
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