The anticancer drug mitoxantrone triggers the formation of ribosome-enriched stress granules independently of the classical translational control pathways

Marta Leśniczak-Staszak; Paulina Pietras; Agnieszka Fedoruk-Wyszomirska; Martino Morici; Mateusz Sowiński; Szymon Krawczyk; Małgorzata Andrzejewska; Eliza Wyszko; Michał Nowicki; Paul J Anderson; Ewelina Gowin; Pavel Ivanov; Daniel N Wilson; Witold Szaflarski

doi:10.1016/j.jmb.2026.169671

The anticancer drug mitoxantrone triggers the formation of ribosome-enriched stress granules independently of the classical translational control pathways

J Mol Biol. 2026 Feb 2:169671. doi: 10.1016/j.jmb.2026.169671. Online ahead of print.

Authors

Affiliations

¹ Department of Histology and Embryology, Poznan University of Medical Sciences, Poznań, Poland; Doctoral School, Poznan University of Medical Sciences, Poznań, Poland.
² Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland; Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland.
³ Institute for Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany.
⁴ Department of Histology and Embryology, Poznan University of Medical Sciences, Poznań, Poland.
⁵ Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland.
⁶ Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
⁷ Department of Health Promotion, Poznan University of Medical Sciences, Poznań, Poland; Department of Immunology, Poznan University of Medical Sciences, Poznań, Poland.
⁸ Department of Histology and Embryology, Poznan University of Medical Sciences, Poznań, Poland. Electronic address: witold@ump.edu.pl.

PMID: 41638308
DOI: 10.1016/j.jmb.2026.169671

Abstract

Mitoxantrone (MIT) is a chemotherapeutic drug widely used for its DNA intercalation and inhibition of topoisomerase. In this work, we show that MIT also affects cytoplasmic RNA-ribosome organization. In human cancer cells, MIT induced stress granules (SGs) that contained large ribosomal subunit proteins, including eL8, together with polyadenylated mRNA. These MIT-induced SGs were different from arsenite-induced SGs: they formed without eIF2α phosphorylation, mTOR inhibition, or 4E-BP1 activity, and they remained stable in the presence of cycloheximide and after drug withdrawal. In vitro assays further demonstrated that MIT promotes ribosome aggregation in a concentration- and salt-dependent manner. Taken together, our results identify a distinct type of ribosome-enriched SGs that form through RNA-ribosome condensation rather than classical translational stress pathways. This mechanism provides a direct example of how a clinically used drug can reorganize cytoplasmic RNA-protein complexes, with possible consequences for mRNA regulation, cancer therapy, and neurodegenerative disease.

Keywords: anticancer drugs; mitoxantrone; ribosome; stress granules.