Skip to Main content Skip to Navigation

Rôle du domaine extracellulaire d’ABCG2 dans l’homéostasie des porphyrines

Abstract : ABCG2 belongs to the ABC-transporter family, involved in drug resistance developed by cells, notably cancer cells. This transporter has also a physiological role of endobiotic detoxification, in particular porphyrins that are essential but potentially toxic molecules. This toxicity implies a specific handle, to avoid them to remain free in solution. In that context, we hypothesized that ABCG2 participate to this detoxification, limiting the intracellular porphyrin accumulation by presenting them to an extracellular partner. We show that ABCG2 transports heme and some of its derivatives and precursors. Interestingly, these porphyrins, unlike other ABCG2 (non-porphyric) substrates, can bind to an extracellular domain, specific of ABCG2, ECL3, 70 residues-long. ECL3 displays affinities for porphyrins in the range of 0.5 to 3.5 μM, high enough to allow their binding after transport. We also show that human serum albumin, implicated in heme detoxification, releases porphyrins bound to ECL3 by a direct interaction with ABCG2. This work established a better comprehension of ABCG2 role in porphyrin and in particular heme homeostasis regulation. In addition, our results contribute to elucidate part of the molecular mechanism by which such regulation is carried out.
Document type :
Complete list of metadata
Contributor : ABES STAR :  Contact
Submitted on : Wednesday, October 2, 2013 - 10:46:10 AM
Last modification on : Tuesday, May 17, 2022 - 3:00:03 PM
Long-term archiving on: : Friday, January 3, 2014 - 6:50:10 AM


Version validated by the jury (STAR)


  • HAL Id : tel-00868903, version 1



Elodie Desuzinges Desuzinges-Mandon. Rôle du domaine extracellulaire d’ABCG2 dans l’homéostasie des porphyrines. Sciences agricoles. Université Claude Bernard - Lyon I, 2010. Français. ⟨NNT : 2010LYO10236⟩. ⟨tel-00868903⟩



Record views


Files downloads