Skip to Main content Skip to Navigation
Journal articles

Inhibition of mitochondrial translation suppresses glioblastoma stem cell growth

Abstract : Glioblastoma stem cells (GSCs) resist current glioblastoma (GBM) therapies. GSCs rely highly on oxidative phosphorylation (OXPHOS), whose function requires mitochondrial translation. Here we explore the therapeutic potential of targeting mitochondrial translation and report the results of high-content screening with putative blockers of mitochondrial ribosomes. We identify the bacterial antibiotic quinupristin/dalfopristin (Q/D) as an effective suppressor of GSC growth. Q/D also decreases the clonogenicity of GSCs in vitro, consequently dysregulating the cell cycle and inducing apoptosis. Cryoelectron microscopy (cryo-EM) reveals that Q/D binds to the large mitoribosomal subunit, inhibiting mitochondrial protein synthesis and functionally dysregulating OXPHOS complexes. These data suggest that targeting mitochondrial translation could be explored to therapeutically suppress GSC growth in GBM and that Q/D could potentially be repurposed for cancer treatment.
Document type :
Journal articles
Complete list of metadata

https://hal-amu.archives-ouvertes.fr/hal-03565947
Contributor : Anita DUMENIL Connect in order to contact the contributor
Submitted on : Friday, February 11, 2022 - 11:59:52 AM
Last modification on : Tuesday, April 12, 2022 - 5:44:06 PM

Links full text

Identifiers

Collections

Citation

Denise Sighel, Michela Notarangelo, Shintaro Aibara, Angela Re, Gianluca Ricci, et al.. Inhibition of mitochondrial translation suppresses glioblastoma stem cell growth. Cell Reports, Elsevier Inc, 2021, 35 (4), pp.109024. ⟨10.1016/j.celrep.2021.109024⟩. ⟨hal-03565947⟩

Share

Metrics

Record views

11