G-quadruplex ligands as potent regulators of lysosomes

Lucille Ferret, Karla Alvarez-Valadez, Jennifer Rivière, Alexandra Muller, Natalia Bohálová, Luo Yu, Lionel Guittat, Vaclav Brázda, Guido Kroemer, Jean Louis Mergny, Mojgan Djavaheri-Mergny

    Research output: Contribution to journalReview articlepeer-review

    7 Citations (Scopus)

    Abstract

    Guanine-quadruplex structures (G4) are unusual nucleic acid conformations formed by guanine-rich DNA and RNA sequences and known to control gene expression mechanisms, from transcription to protein synthesis. So far, a number of molecules that recognize G4 have been developed for potential therapeutic applications in human pathologies, including cancer and infectious diseases. These molecules are called G4 ligands. When the biological effects of G4 ligands are studied, the analysis is often limited to nucleic acid targets. However, recent evidence indicates that G4 ligands may target other cellular components and compartments such as lysosomes and mitochondria. Here, we summarize our current knowledge of the regulation of lysosome by G4 ligands, underlying their potential functional impact on lysosome biology and autophagic flux, as well as on the transcriptional regulation of lysosomal genes. We outline the consequences of these effects on cell fate decisions and we systematically analyzed G4-prone sequences within the promoter of 435 lysosome-related genes. Finally, we propose some hypotheses about the mechanisms involved in the regulation of lysosomes by G4 ligands.

    Original languageEnglish
    Pages (from-to)1901-1915
    Number of pages15
    JournalAutophagy
    Volume19
    Issue number7
    DOIs
    Publication statusPublished - 1 Jan 2023

    Keywords

    • Autophagy
    • TFEB
    • guanine-quadruplex
    • lysosome membrane permeabilization
    • transcriptional regulation

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