P034 Effects of a tripeptidyl peptidase

P034 Effects of a tripeptidyl peptidase-1 deciency on the
mitochondrial population of human broblasts
Guillaume VAN BEERSEL(1) Stéphane DEMINE(1)
Isabelle HAMER(2) Michel JADOT(2) and
Thierry ARNOULD(1)
(1) URBC, Unité de Recherche en Biochimie Cellulaire,
Faculty of Sciences (2) URPhyM, Unité de Recherche
en Physiologie Moléculaire, Laboratoire de Chimie
Physiologique, Faculty of Medicine, Facultés Universitaires
Notre-Dame de la Paix, Rue de Bruxelles, 61, 5000 Namur,
Belgium
Late Infantile Ceroid Lipofuscinosis (LINCL) is a neurodegen-
erative disorder resulting from a deciency of the tripeptidyl
peptidase-1 (TPP-1) leading to an accumulation of autouores-
cent ceroid lipopigment enclosed within lysosomal structures.
Knowledge about the molecular mechanisms leading to the
numerous pathophysiological consequences of LINCL and cell
responses to this lysosomal storage disorder remain largely
unknown, but they might affect the function of other organelles
such as ER and mitochondria.
In this study, we investigated the putative effects of the TPP-1
deciency on the mitochondrial population of human broblasts.
We show that neither the abundance of mitochondria nor the
mitochondrial membrane potential is modied in TPP-1 decient
cells. However, the morphology of this organelle is changed as
the mitochondrial network seems to be more fragmented. This
could be explained by the increase in the mitochondrial transloca-
tion of DRP-1 (Dynamin Related Protein-1). This fragmentation is
accompanied by a decrease in the mitochondrial calcium buffering
capacity in response to an increase in cytosolic calcium concen-
tration.