TY - JOUR
T1 - G-quadruplex ligands as potent regulators of lysosomes
AU - Ferret, Lucille
AU - Alvarez-Valadez, Karla
AU - Rivière, Jennifer
AU - Muller, Alexandra
AU - Bohálová, Natalia
AU - Yu, Luo
AU - Guittat, Lionel
AU - Brázda, Vaclav
AU - Kroemer, Guido
AU - Mergny, Jean Louis
AU - Djavaheri-Mergny, Mojgan
N1 - Publisher Copyright:
© 2023 Inserm.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - 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.
AB - 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.
KW - Autophagy
KW - TFEB
KW - guanine-quadruplex
KW - lysosome membrane permeabilization
KW - transcriptional regulation
UR - http://www.scopus.com/inward/record.url?scp=85147680783&partnerID=8YFLogxK
U2 - 10.1080/15548627.2023.2170071
DO - 10.1080/15548627.2023.2170071
M3 - Review article
C2 - 36740766
AN - SCOPUS:85147680783
SN - 1554-8627
VL - 19
SP - 1901
EP - 1915
JO - Autophagy
JF - Autophagy
IS - 7
ER -