bims-cytox1 Biomed News
on Cytochrome oxidase subunit 1
Issue of 2026–05–31
two papers selected by
Gavin McStay, Liverpool John Moores University
  1. Compound Heterozygous COA7 Variants Presenting With Childhood-Onset Axonal Neuropathy in 2 Siblings.
  2. Copper depletion boosts CNS leukemia therapy by inhibiting nucleotide synthesis through impairment of mitochondrial complex IV activity.
  1. Neurol Genet. 2026 Jun;12(3): e200394
    Compound Heterozygous COA7 Variants Presenting With Childhood-Onset Axonal Neuropathy in 2 Siblings.
    Gianpaolo Cicala, Elisa Rolleri, Beatrice Berti, Marco Luigetti, Nicola Forcina, Marianna Villa, Anna Capasso, Chiara Arpaia, Martina Malaspina, Fabiana Fattori, Luca Bosco, Guido Primiano, Antonio Novelli, Teresa Rizza, Enrico Bertini, Marika Pane, Eugenio Mercuri.
       Objectives: Variants in COA7 (cytochrome c oxidase assembly factor 7) are a rare cause of mitochondrial disease, with limited clinical descriptions and phenotypic variability. We describe 2 siblings carrying compound heterozygous COA7 variants, one of which (c.457C>T; p.Leu153Phe) is novel. Both presented with early-onset, slowly progressive axonal sensorimotor neuropathy, with differences in severity and associated features.
    Methods: Patients were identified based on clinical presentation and evaluated through longitudinal neurologic, neurophysiologic, genetic, biochemical, and neuroimaging assessments.
    Results: The elder brother developed symptoms at age 12, including muscle cramps, tremors, and falls, whereas the sister showed motor impairment with difficulty walking and running from age 5, along with more prominent cerebellar involvement. Shared features included distal weakness, impaired gait, areflexia, tremor, pes cavus, sensory disturbances, and cognitive difficulties, which were milder in the older brother. Nerve conduction studies demonstrated axonal sensorimotor polyneuropathy. Genetic analysis identified 2 compound heterozygous COA7 variants. Skin biopsy revealed reduced mitochondrial complex IV activity. Brain MRI findings were unremarkable in both siblings.
    Discussion: These cases expand the clinical spectrum of COA7-related disorders and illustrate the potential for intrafamilial phenotypic variability. The identification of a novel variant and extended clinical follow-up provide further insight into the features associated with COA7 variants.
    DOI:  https://doi.org/10.1212/NXG.0000000000200394
  2. Nat Cancer. 2026 May 25.
    Copper depletion boosts CNS leukemia therapy by inhibiting nucleotide synthesis through impairment of mitochondrial complex IV activity.
    Alan Y L Wong, Jacob W Myers, Gyan Prakash, Alice Ma, Jeannette R Brook, Boryana Petrova, Baran Bulut, Ralph White, Catherine Merz, Maeve de Souza, Adam G Maynard, Peng Wang, Amy Yu, Nancy K Pohl, Michal Weitman, Lewis B Silverman, Kimberly Stegmaier, L Stirling Churchman, Peter D Cole, Donita C Brady, Naama Kanarek.
      The nutrient-sparse cerebrospinal fluid (CSF) poses a major challenge to spreading cancer cells. Despite this challenge, leukemia cells spread to the CSF, requiring aggressive central nervous system (CNS)-directed treatment that can lead to neurotoxicity. Here we used a targeted in vivo CRISPR screen to identify nutritional dependencies of systemic and CNS acute lymphoblastic leukemia (ALL). We show that copper depletion, either by genetic deletion of the transporter SLC31A1 or by dietary intervention, slows the growth of both systemic and CNS leukemia in a xenograft model. Mechanistically, copper depletion inhibits complex IV and nucleotide synthesis to slow the growth of leukemia cells. Furthermore, dietary depletion of copper combined with the standard-of-care therapy methotrexate inhibits leukemia progression in cell-line-derived and patient-derived xenograft models. Our findings identify copper as an actionable micronutrient to disrupt nucleotide synthesis in ALL and proposes copper depletion as a way to boost leukemia therapy in the hard-to-treat CNS.
    DOI:  https://doi.org/10.1038/s43018-026-01177-4
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