bims-cytox1 Biomed News
on Cytochrome oxidase subunit 1
Issue of 2026–09–06
two papers selected by
Gavin McStay, Liverpool John Moores University
  1. Copper, cuproptosis, and cancer: biology concepts of a novel cell death.
  2. SLIRP differentially modulates RNA binding of pathogenic LRPPRC variants.
  1. Apoptosis. 2026 Sep 03. pii: 223. [Epub ahead of print]31(9):
    Copper, cuproptosis, and cancer: biology concepts of a novel cell death.
    Reza Eshraghi, Nastaran Hosseini, Mohammad Sepehr Yazdani, Shirin Badihi, Pedram Pirmoradian, Ashkan Bahrami, Bahar Darouei, Shayan Ghanouni, Alfred K Lam, Michael R Hamblin.
      Copper is an essential trace element required for mitochondrial respiration, redox regulation, iron metabolism, and cellular signalling, but excessive or mislocalised copper can be cytotoxic. Cuproptosis is a recently identified form of regulated cell death in which copper binds to lipoylated mitochondrial proteins, promotes their aggregation, destabilises iron-sulfur cluster proteins, and induces mitochondrial proteotoxic stress. Copper therefore has context-dependent roles in cancer. Physiological copper supports tumour metabolism, angiogenesis, extracellular-matrix remodelling, and selected oncogenic signalling pathways, whereas therapeutic copper depletion can inhibit copper-dependent tumour processes. Conversely, copper ionophores and related approaches may increase intracellular copper sufficiently to induce cuproptosis in metabolically susceptible cancer cells. This review describes systemic and intracellular copper homeostasis, including intestinal absorption, intracellular trafficking, mitochondrial copper distribution, storage, and export. Particular attention is given to CTR1/SLC31A1, the functionally distinct copper-transporting ATPases ATP7A and ATP7B, metallothioneins, copper chaperones, and cytochrome c oxidase assembly factors. We also examine how cancer cells reprogramme copper handling to support proliferation, angiogenesis, metastasis, and immune evasion. Finally, we discuss the molecular basis of cuproptosis, including the roles of FDX1, FDXR, LIAS, DLAT, mitochondrial respiration, protein lipoylation, and iron-sulfur cluster destabilisation. Current evidence indicates that cuproptosis susceptibility varies among tumour types and depends on copper handling, mitochondrial metabolic state, and the integrity of the protein-lipoylation machinery. Defining these determinants will be necessary for the development of tumour-selective copper-targeted therapies.
    Keywords:  Cancer treatment; Copper; Copper homeostasis; Cuproptosis; Mitochondrial dysfunction
    DOI:  https://doi.org/10.1007/s10495-026-02432-w
  2. NAR Mol Med. 2026 Jul;3(3): ugag040
    SLIRP differentially modulates RNA binding of pathogenic LRPPRC variants.
    Louise Lambert, Urška Rovšnik, Amandine Moretton, Katarina Johansson, Mãdãlina Sãcultanu, Mathilde Chéron, Adèle Porcan, Bertil Macao, Siet van den Wildenberg, Xuefeng Zhu, Maria Falkenberg, Géraldine Farge.
      The LRPPRC/SLIRP complex is a key post-transcriptional regulator of mitochondrial gene expression, stabilizing mitochondrial mRNAs and promoting their polyadenylation and translation. Mutations in LRPPRC cause mitochondrial disorders, including Leigh syndrome French-Canadian type (LSFC), primarily affecting oxidative phosphorylation. Here, we examined the RNA-binding properties of wild-type LRPPRC and three pathogenic variants (A354V, K909del, and R1276_K1300del) using electrophoretic mobility shift assays, acoustic force spectroscopy, and AlphaFold 3 modeling. All three mutations reduced intrinsic RNA binding, with R1276_K1300del showing no detectable interaction in the absence of SLIRP. Remarkably, SLIRP restored RNA binding of this mutant to near wild-type levels, likely through conformational stabilization, as supported by single-molecule and structural analyses. These findings highlight SLIRP's critical role in modulating LRPPRC function and suggest that enhancing SLIRP activity represents a potential therapeutic strategy for LRPPRC-related mitochondrial disorders.
    DOI:  https://doi.org/10.1093/narmme/ugag040
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