Poster Presentation 10th Australian Peptide Conference 2013

Peptides Derived from the Transmembrane Domain of Bcl-2 Proteins as Potential Mitochondrial Priming Tools (#153)

Vicente Andreu-Fernández 1 , Ainhoa Genoves 1 2 , Tzong-Hsien (John) Lee 3 , Matthew Stellato 3 , Federico Lucantoni 1 , Ismael Mingarro 4 , Mibel Aguilar 3 , Enrique Pérez-Payá 1 2
  1. Laboratory of Peptide and Protein Chemistry, Centro de Investigación Príncipe Felipe, Valencia, Spain
  2. Instituto de Biomedicina de Valencia, Valencia, Spain
  3. Biochemistry and Molecular Biology, Monash university, Clayton, VIC, Australia
  4. Departament de Bioquímica i Biologia Molecular, Universitat de València, Burjassot, Spain

The Bcl-2 family of proteins is crucial for apoptosis regulation. The Bcl-2 proteins are synthesized in cytosolic ribosomes before reaching the lipid bilayer, where they insert through a specific C-terminal anchoring transmembrane domain. The members of this family of proteins target distinct intracellular membranes, including the mitochondrial outer membrane where they interact in order to determine cell fate. While the mitochondrial membrane has been proposed to actively participate in these protein-protein interactions, the influence of the transmembrane domain in the membrane-mediated interactions is poorly understood. The putative transmembrane domain (TMD) of anti-apoptotic (Bcl-2, Bcl-xL, Bcl-w and Mcl-1) and pro-apoptotic (Bax, Bak) members were selected and synthetic peptides (TMDpepts) derived from the respective domains were synthesized and characterized. TMDpepts showed higher affinity to interact with mitochondria-like than with plasma membrane-like model bilayers and higher binding correlated with greater membrane perturbation. These TMDpepts were effective as tools to prepare mitochondria for apoptosis by sensitizing human cervix adenocarcinoma cells to chemotherapeutic agents.