bims-cytox1 Biomed News
on Cytochrome oxidase subunit 1
Issue of 2026–06–28
two papers selected by
Gavin McStay, Liverpool John Moores University
  1. Proteolytic coordination of the OXPHOS Life Cycle.
  2. Variable mitochondrial phenotypes and reduced complex IV assembly factor SCO2 in LRRK2-G2019S fibroblasts.
  1. Biochem J. 2026 Jul 08. 483(7): 1253-1280
    Proteolytic coordination of the OXPHOS Life Cycle.
    Nataliia Nechytailo, Karolina Szczepanowska.
      The mitochondrial oxidative phosphorylation (OXPHOS) system consists of multimeric, highly ordered protein complexes critical for energy production and metabolic wiring in the cell. Recent discoveries in mitochondrial proteolysis, facilitated by advances in proteomic approaches, have transformed the view of mitochondrial proteases from a simple quality-control system into a dynamically coordinated network of enzymes that actively shape the status of the OXPHOS machinery. Mapping OXPHOS-associated proteolytic circuits has uncovered specialized functions of individual proteases and identified key interaction sites. The present review outlines how mitochondrial proteases regulate the OXPHOS life cycle: expression, delivery, assembly, long-term maintenance, and disposal of mitochondrial respiratory complexes. We summarize past findings and highlight emerging concepts, including asynchronous OXPHOS turnover, cofactor-driven proteolysis, and bioenergetics-coupled degradation. Progress in these areas will deepen our understanding of how proteases coordinate the OXPHOS life cycle.
    Keywords:  mitochondria; mitochondrial proteases; mitochondrial respiratory complexes; oxidative phosphorylation; regulatory proteolysis; turnover
    DOI:  https://doi.org/10.1042/BCJ20250120
  2. Sci Rep. 2026 Jun 25.
    Variable mitochondrial phenotypes and reduced complex IV assembly factor SCO2 in LRRK2-G2019S fibroblasts.
    Ruby Wallis, Ella Simmonite, Harry Cooper, Olivia Cracknell, Amandeep Kaur, Elizabeth J New, Jan Aasly, Oliver Bandmann, Heather Mortiboys.
      LRRK2-G2019S is the most common pathogenic LRRK2 mutation which accounts for up to 13% of cases of familial Parkinson's disease. The LRRK2-G2019S mutation has incomplete penetrance which increases with age. Molecular mechanisms which contribute to the disease status in LRRK2-G2019S mutation carriers are yet to be fully defined. Here, we aimed to further investigate the specific mitochondrial effects of LRRK2-G2019S penetrance in a cohort of patient-derived fibroblasts from manifesting and non-manifesting LRRK2-G2019S carriers compared to controls to further elucidate the pathogenic mechanism of the mutation. We find a significant reduction of 50% in the expression of the complex IV assembly factor SCO2 in LRRK2-G2019S manifesting fibroblasts. In contrast, SCO2 levels remained similar to controls in non-manifesting LRRK2-G2019S carriers. A small reduction in complex IV subunit expression accompanied this reduction in SCO2 in manifesting LRRK2-G2019S carriers. Despite the role of SCO2 in copper incorporation into complex IV, we identified no differences in the unbound mitochondrial copper content in a limited number of manifesting or non-manifesting LRRK2-G2019S carriers compared to controls. However, LRRK2-G2019S carriers exhibit variable cellular phenotypes in mitochondrial morphology, mitochondrial membrane potential and cellular ATP or ROS production which does not differ significantly between manifesting and non-manifesting carriers. We conclude that mitochondrial complex IV deficiency could be a pathogenic mechanism of the LRRK2-G2019S mutation which may be attributed to a reduction in SCO2, however there is evident heterogeneity in the cellular phenotype of LRRK2-G2019S carriers which may suggest underlying compensatory mechanisms.
    Keywords:  G2019S mutation; Leucine-rich repeat kinase-2 (LRRK2); Manifesting; Mitochondria; Non-manifesting; Parkinson’s disease; Penetrance
    DOI:  https://doi.org/10.1038/s41598-026-58797-0
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