bims-resufa Biomed News
on Respiratory supercomplex factors
Issue of 2024‒02‒25
two papers selected by
Gavin McStay, Liverpool John Moores University
  1. Euglena's atypical respiratory chain adapts to the discoidal cristae and flexible metabolism.
  2. The Structure of the Cardiac Mitochondria Respirasome Is Adapted for the β-Oxidation of Fatty Acids.
  1. Nat Commun. 2024 Feb 22. 15(1): 1628
    Euglena's atypical respiratory chain adapts to the discoidal cristae and flexible metabolism.
    Zhaoxiang He, Mengchen Wu, Hongtao Tian, Liangdong Wang, Yiqi Hu, Fangzhu Han, Jiancang Zhou, Yong Wang, Long Zhou.
      Euglena gracilis, a model organism of the eukaryotic supergroup Discoba harbouring also clinically important parasitic species, possesses diverse metabolic strategies and an atypical electron transport chain. While structures of the electron transport chain complexes and supercomplexes of most other eukaryotic clades have been reported, no similar structure is currently available for Discoba, limiting the understandings of its core metabolism and leaving a gap in the evolutionary tree of eukaryotic bioenergetics. Here, we report high-resolution cryo-EM structures of Euglena's respirasome I + III2 + IV and supercomplex III2 + IV2. A previously unreported fatty acid synthesis domain locates on the tip of complex I's peripheral arm, providing a clear picture of its atypical subunit composition identified previously. Individual complexes are re-arranged in the respirasome to adapt to the non-uniform membrane curvature of the discoidal cristae. Furthermore, Euglena's conformationally rigid complex I is deactivated by restricting ubiquinone's access to its substrate tunnel. Our findings provide structural insights for therapeutic developments against euglenozoan parasite infections.
    DOI:  https://doi.org/10.1038/s41467-024-46018-z
  2. Int J Mol Sci. 2024 Feb 18. pii: 2410. [Epub ahead of print]25(4):
    The Structure of the Cardiac Mitochondria Respirasome Is Adapted for the β-Oxidation of Fatty Acids.
    Alexander V Panov.
      It is well known that in the heart and kidney mitochondria, more than 95% of ATP production is supported by the β-oxidation of long-chain fatty acids. However, the β-oxidation of fatty acids by mitochondria has been studied much less than the substrates formed during the catabolism of carbohydrates and amino acids. In the last few decades, several discoveries have been made that are directly related to fatty acid oxidation. In this review, we made an attempt to re-evaluate the β-oxidation of long-chain fatty acids from the perspectives of new discoveries. The single set of electron transporters of the cardiac mitochondrial respiratory chain is organized into three supercomplexes. Two of them contain complex I, a dimer of complex III, and two dimers of complex IV. The third, smaller supercomplex contains a dimer of complex III and two dimers of complex IV. We also considered other important discoveries. First, the enzymes of the β-oxidation of fatty acids are physically associated with the respirasome. Second, the β-oxidation of fatty acids creates the highest level of QH2 and reverses the flow of electrons from QH2 through complex II, reducing fumarate to succinate. Third, β-oxidation is greatly stimulated in the presence of succinate. We argue that the respirasome is uniquely adapted for the β-oxidation of fatty acids. The acyl-CoA dehydrogenase complex reduces the membrane's pool of ubiquinone to QH2, which is instantly oxidized by the smaller supercomplex, generating a high energization of mitochondria and reversing the electron flow through complex II, which reverses the electron flow through complex I, increasing the NADH/NAD+ ratio in the matrix. The mitochondrial nicotinamide nucleotide transhydrogenase catalyzes a hydride (H-, a proton plus two electrons) transfer across the inner mitochondrial membrane, reducing the cytosolic pool of NADP(H), thus providing the heart with ATP for muscle contraction and energy and reducing equivalents for the housekeeping processes.
    Keywords:  heart mitochondria; oxidative phosphorylation; respirasome; respiratory chain; tricarboxylic acid cycle; ubiquinol; ubiquinone; β-oxidation of fatty acids
    DOI:  https://doi.org/10.3390/ijms25042410
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