Organelle cross-talk : a non lethal endoplasmic reticulum stress or a lysosomal dysfunction triggers mitochondria fragmentation

Alterations of these crosstalks might be involved in several biological processes including the regulation of mitochondrial bioenergetics, control of cell death pathways and more and more seem to play a role in metabolic disorders, cancers and neurodegenerative diseases. We study the mechanisms by which a sublethal ER stress/UPR induced by thapsigargin (a SERCA pump inhibitor) or brefeldin A (an inhibitor of protein transport from ER to Golgi) triggers the fragmentation of mitochondria and the consequences of thse changes on the biology of the cell in the adaptive response to the ER stress (Vannuvel et al., J. Cell Physiol., revision).         

In addition, other organelle crosstalks between mitochondria and lysosomes were also investigated as recent data suggests that the pathogenesis of NCL (neuronal ceroid lipofuscinoses) is also associated with the appearance of fragmented mitochondria.  We showed that fibroblasts that are deficient for the TPP-1 (tripeptidyl peptidase-1), a lysosomal hydrolase encoded by the gene mutated in the LINCL (late infantile NCL, CLN2 form), also exhibit a fragmented mitochondrial network (Van Beersel et al., Biosci. Rep., 2013 ; Van Beersel et al., The Open Pathology Journal, 2013). While maturation and trafficking of lysosomal enzymes are also affected in cells in mtDNA-depleted cells (Hamer et al., Biol Cell, 2009).