bims-cytox1 2025-05-04 papers

on Cytochrome oxidase subunit 1

Issue of 2025–05–04
two papers selected by
Gavin McStay, Liverpool John Moores University

The copper ionophore disulfiram improves mitochondrial function in various yeast and human cellular models of mitochondrial diseases.
TACO1 facilitates the proliferation and migration of gastric cancer cells via Notch1/Hes1 signaling and is associated with immune cell infiltration.

Hum Mol Genet. 2025 Apr 29. pii: ddaf061. [Epub ahead of print]

The copper ionophore disulfiram improves mitochondrial function in various yeast and human cellular models of mitochondrial diseases.

Claire Almyre, Nolwenn Bounaix, François Godard, Olivier R Baris, Anne-Louise Cayer, Elodie Sardin, Marine Bouhier, Anaïs Hoarau, Laetitia Dard, Jérémy Richard, Vanessa Bergeron, Aurélie Renaud, Nadege Loaëc, Naïg Gueguen, Valérie Desquiret-Dumas, Bénédicte Lelievre, Aurore Inisan, Cristina Panozzo, Genevève Dujardin, Marc Blondel, Agnes Rötig, Véronique Paquis-Flucklinger, Stéphane Azoulay, Nathalie Bonnefoy, Carole H Sellem, Agnès Delahodde, Vincent Procaccio, Déborah Tribouillard-Tanvier.

  The copper ionophore disulfiram (DSF) is commonly used to treat chronic alcoholism and has potential anti-cancer activity. Using a yeast-based screening assay of FDA-approved compounds, DSF was herein identified for its ability to improve oxidative phosphorylation-dependent growth of various yeast models of mitochondrial diseases caused by a wide range of defects in ATP synthase, complexes III and IV, cardiolipin remodeling, maintenance and translation of the mitochondrial genome. This compound also showed beneficial effects in cells derived from patients suffering from Barth or MELAS syndromes, two mitochondrial diseases associated respectively with a lack in cardiolipin remodeling and protein synthesis inside the organelle. We provide evidence that the rescuing activity of DSF results from its ability to transport copper ions across biological membranes. Indeed, other copper ionophores (pyrithione and elesclomol) and supplementation of the growth media with copper ions had also beneficial effects in yeast and human cells with dysfunctional mitochondria. Our data suggest that the copper-dependent rescuing activity in these cells results from a better capacity to assemble cytochrome c oxidase. Altogether, our findings hold promise for the development of new therapeutic strategies for mitochondrial disorders.

Keywords:  Mitochondrial diseases; copper; disulfiram; drug repositioning; oxidative phosphorylation

DOI:  https://doi.org/10.1093/hmg/ddaf061
Exp Cell Res. 2025 Apr 25. pii: S0014-4827(25)00170-3. [Epub ahead of print]448(2): 114574

TACO1 facilitates the proliferation and migration of gastric cancer cells via Notch1/Hes1 signaling and is associated with immune cell infiltration.

Na Li, Zijie Wei, Xiang Li, Jiayu Jian, Lulu Zhou, Siqi Wang, Miao Chen, Yu Cheng.

  Translational activator of cytochrome c oxidase 1 (TACO1) is a mitochondrial RNA-binding protein playing a fundamental role in mitochondrial translation. However, no studies to date have evaluated changes in the expression, biological functions, and potential molecular mechanisms of action of TACO1 in gastric cancer. Therefore, we investigated the clinical significance, biological function, and immune system modulation associated with TACO1 in gastric cancer. We found that TACO1 expression was upregulated in gastric cancer and associated with poor prognosis. Mechanistically, TACO1 facilitated gastric cancer cell proliferation and migration through modulation of the Notch1/Hes1 signaling pathways. Moreover, the change in TACO1 expression affected multiple immunological components to regulate the generation of an immunosuppressive tumor microenvironment (TME). In conclusion, we first report on the role of TACO1 in gastric cancer, with findings suggesting that TACO1 could represent a promising prognostic and immunological biomarker for gastric cancer.

Keywords:  Gastric cancer; Notch1/Hes1; RNA-Binding protein; TACO1

DOI:  https://doi.org/10.1016/j.yexcr.2025.114574