Rôle de la préséniline 2 dans le potential de membrane mitochondrial

Details

Supervisors

Kienlen-Campard, Pascal ; Marinangeli, Claudia

Faculty

Faculté de médecine et médecine dentaire

Degree label

Mémoire de master en sciences biomédicales (finalité spécialisée)

Abstract

The Presenilins (PSI or PS2) are the catalytic subunits of the y-secretase. The y­ secretase is a tetrameric complex that performs the second step of the amyloidogenic metabolism of the Amyloid Precursor Protein (APP), leading to the release of the p-amyloid peptide (Ap) - the main component of the senile plaques found in Alzheimer's disease (AD).AP is essentially produced by PSl-dependent y-secretases complexes, and our understanding of PS2 function is scarce. In addition to y-secretase activity, presenilins were found to be involved in ceUular calcium homeostasis.Interestingly, recent studies reported that presenilins are enriched in particular domains of the endoplasmic reticulum (ER) forming contacts with the outer mitochondrial membrane and called ER Mitochondria-Associated Membranes (ER-MAM). This structure is gating ions and molecules exchanges between mitochondria and ER Our first objective was to characterize the "mitochondrial phenotype" of PS deficient cells. By combining fluorescent cell imaging and FACS analysis, we found that the mitochondrial membrane potential is increased in PS2 KO cells so that PS2 bas a protective effect.We generated PS2KO rescue cells for PS2 wild type and PS2 mutant D, where the catalytic aspartate residue is mutated, leading to an inactive form of PS2. We studied the cellular role of our different cell lines, in particular in ER-MAM formation and subsequent mitochondrial function.