Interplay between Cellular Uptake, Intracellular Localization and the Cell Death Mechanism in Triphenylamine-Mediated Photoinduced Cell Death.
Fiche publication
Date publication
avril 2020
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr FROCHOT Céline
Tous les auteurs :
Chennoufi R, Trinh ND, Simon F, Bordeau G, Naud-Martin D, Moussaron A, Cinquin B, Bougherara H, Rambaud B, Tauc P, Frochot C, Teulade-Fichou MP, Mahuteau-Betzer F, Deprez E
Lien Pubmed
Résumé
Triphenylamines (TPAs) were previously shown to trigger cell death under prolonged one- or two-photon illumination. Their initial subcellular localization, before prolonged illumination, is exclusively cytoplasmic and they translocate to the nucleus upon photoactivation. However, depending on their structure, they display significant differences in terms of precise initial localization and subsequent photoinduced cell death mechanism. Here, we investigated the structural features of TPAs that influence cell death by studying a series of molecules differing by the number and chemical nature of vinyl branches. All compounds triggered cell death upon one-photon excitation, however to different extents, the nature of the electron acceptor group being determinant for the overall cell death efficiency. Photobleaching susceptibility was also an important parameter for discriminating efficient/inefficient compounds in two-photon experiments. Furthermore, the number of branches, but not their chemical nature, was crucial for determining the cellular uptake mechanism of TPAs and their intracellular fate. The uptake of all TPAs is an active endocytic process but two- and three-branch compounds are taken up via distinct endocytosis pathways, clathrin-dependent or -independent (predominantly caveolae-dependent), respectively. Two-branch TPAs preferentially target mitochondria and photoinduce both apoptosis and a proper necrotic process, whereas three-branch TPAs preferentially target late endosomes and photoinduce apoptosis only.
Référence
Sci Rep. 2020 Apr 23;10(1):6881