bims-cytox1 Biomed News
on Cytochrome oxidase subunit 1
Issue of 2025–08–17
two papers selected by
Gavin McStay, Liverpool John Moores University



  1. J Inorg Biochem. 2025 Aug 08. pii: S0162-0134(25)00205-3. [Epub ahead of print]273 113025
      The study of transition metals and their role in living matter has a long and distinguished history. This field, today referred to as Bioinorganic Chemistry, has evolved into a vibrant area of research. Progress is fueled by four main factors: (1) the use of high-tech spectroscopy to explore the structural and dynamic properties of molecules, (2) the molecular engineering and design of artificial enzymes, (3) the rapid determination of high-resolution structures of proteins and large protein complexes, and (4) the significant advancements in computational chemistry. First, I will take the reader on a brief journey "Meeting Harry B. Gray". Hereafter, significant basic work in the laboratory and crucial key findings will be presented that have enhanced our understanding of the structural and functional features of notable metalloenzymes with unique catalytic sites: (i) the blue type-1 Cu center and the trinuclear O2 activating Cu cluster in ascorbate oxidase, (ii) the purple mixed-valent [Cu1.5+(CyS-)2Cu1.5+] copperA electron transfer center in nitrous oxide reductase and cytochrome c oxidase, (iii) intraprotein control of electron transfer rates by allosteric interactions within the green nitrite reductase cytochrome cd1, and (iv) active site structure and reaction mechanism of the red pentaheme cytochrome c nitrite reductase based on crystallographic identification of reaction intermediates and density functional calculations. This topic is particularly apt for honoring Harry B. Gray, who has made numerous seminal contributions to modern Inorganic Chemistry, especially as we celebrate his 90th birthday.
    Keywords:  Bioinorganic chemistry; Blue Copper; Copper A; Electron transfer; Heme enzyme; Pulse radiolysis
    DOI:  https://doi.org/10.1016/j.jinorgbio.2025.113025
  2. Cell. 2025 Aug 07. pii: S0092-8674(25)00811-6. [Epub ahead of print]
      Nearly all mitochondrial proteins are translated on cytosolic ribosomes. How these proteins are subsequently delivered to mitochondria remains poorly understood. Using selective ribosome profiling, we show that nearly 20% of mitochondrial proteins can be imported cotranslationally in human cells. Cotranslational import requires an N-terminal presequence on the nascent protein and contributes to localized translation at the mitochondrial surface. This pathway does not favor membrane proteins but instead prioritizes large, multi-domain, topologically complex proteins, whose import efficiency is enhanced when targeted cotranslationally. In contrast to the early onset of cotranslational protein targeting to the endoplasmic reticulum (ER), the presequence on mitochondrial proteins is inhibited from initiating targeting early during translation until a large globular domain emerges from the ribosome. Our findings reveal a multi-layered protein sorting strategy that controls the timing and specificity of mitochondrial protein targeting.
    Keywords:  NAC; TOM complex; cotranslational protein import; localized translation; mitochondria; mitochondrial targeting sequence; nascent polypeptide-associated complex; protein folding; protein targeting; ribosome profiling
    DOI:  https://doi.org/10.1016/j.cell.2025.07.021