bims-cytox1 2024-09-22 papers

Issue of 2024‒09‒22
two papers selected by
Gavin McStay, Liverpool John Moores University

Sci Rep. 2024 09 17. 14(1): 21678

Characterization of Shy1, the Schizosaccharomyces pombe homolog of human SURF1.

Ying Luo, Yuanqi Xu, Fawad Ahmad, Gang Feng, Ying Huang.

Cytochrome c oxidase (complex IV) is the terminal enzyme in the mitochondrial respiratory chain. As a rare neurometabolic disorder caused by mutations in the human complex IV assembly factor SURF1, Leigh Syndrome (LS) is associated with complex IV deficiency. In this study, we comprehensively characterized Schizosaccharomyces pombe Shy1, the homolog of human SURF1. Bioinformatics analysis revealed that Shy1 contains a conserved SURF1 domain that links to the biogenesis of complex IV and shares high structural similarity with its homologs in Saccharomyces cerevisiae and humans. Our study showed that Shy1 is required for the expression of mtDNA-encoded genes and physically interacts with structural subunits and assembly factors of complex IV. Interestingly, Rip1, the subunit of ubiquinone-cytochrome c oxidoreductase or cytochrome bc1 complex (complex III), can also co-immunoprecipitate with Shy1, suggesting Shy1 may be involved in the assembly of the mitochondrial respiratory chain supercomplexes. This conclusion is further corroborated by our BN-PAGE analysis. Unlike its homologs, deletion of shy1 does not critically disrupt respiratory chain assembly, indicating the presence of the compensatory mechanism(s) within S. pombe that ensure mitochondrial functionality. Collectively, our investigation elucidates that Shy1 plays a pivotal role in the sustainability of the regular function of mitochondria by participating in the assembly of complex IV in S. pombe.

Keywords: Schizosaccharomyces pombe ; SURF1; Shy1; cytochrome c oxidase; mitochondria

DOI: https://doi.org/10.1038/s41598-024-72681-9

J Inorg Biochem. 2024 Sep 08. pii: S0162-0134(24)00254-X. [Epub ahead of print]262 112730

Structural and functional mechanisms of cytochrome c oxidase.

Denis L Rousseau, Izumi Ishigami, Syun-Ru Yeh.

Cytochrome c oxidase (CcO) is the terminal enzyme in the electron transfer chain in mitochondria. It catalyzes the four-electron reduction of O2 to H2O and harnesses the redox energy to drive unidirectional proton translocation against a proton electrochemical gradient. A great deal of research has been conducted to comprehend the molecular properties of CcO. However, the mechanism by which the oxygen reduction reaction is coupled to proton translocation remains poorly understood. Here, we review the chemical properties of a variety of key oxygen intermediates of bovine CcO (bCcO) revealed by time-resolved resonance Raman spectroscopy and the structural features of the enzyme uncovered by serial femtosecond crystallography, an innovative technique that allows structural determination at room temperature without radiation damage. The implications of these data on the proton translocation mechanism are discussed.

Keywords: Bioenergetics; Cytochrome c oxidase; Oxygen reduction chemistry; Proton translocation; Resonance Raman spectroscopy; Serial femtosecond X-ray crystallography

DOI: https://doi.org/10.1016/j.jinorgbio.2024.112730