Université de Fribourg

Granzyme B attenuates bacterial virulence by targeting secreted factors

López León, Diego ; Matthey, Patricia ; Fellay, Isabelle ; Blanchard, Marianne ; Martinvalet, Denis ; Mantel, Pierre-Yves ; Filgueira, Luis ; Walch, Michael

In: iScience, 2020, vol. 23, no. 3, p. 100932

Pathogenic bacteria secrete virulence factors that interact with the human host to establish infections. The human immune system evolved multiple mechanisms to fight bacterial invaders, including immune proteases that were demonstrated to contribute crucially to antibacterial defense. Here we show that granzyme B degrades multiple secreted virulence mediators from Listeria monocytogenes,...

Université de Fribourg

Granzyme B enters the mitochondria in a Sam50-, Tim22- and mtHsp70-dependent manner to induce apoptosis

Chiusolo, Valentina ; Jacquemin, Guillaume ; Bassoy, Esen Yonca ; Vinet, Laurent ; Liguori, Lavinia ; Walch, Michael ; Kozjak-Pavlovic, Vera ; Martinvalet, Denis

In: Cell Death & Differentiation, 2017, vol. 24, no. 4, p. 747–758

We have found that granzyme B (GB)-induced apoptosis also requires reactive oxygen species resulting from the alteration of mitochondrial complex I. How GB, which does not possess a mitochondrial targeting sequence, enter this organelle is unknown. We show that GB enters the mitochondria independently of the translocase of the outer mitochondrial membrane complex, but requires instead Sam50,...

Université de Fribourg

Granzyme B-induced mitochondrial ROS are required for apoptosis

Jacquemin, G. ; Margiotta, D. ; Kasahara, A. ; Bassoy, E. Y. ; Walch, Michael ; Thiery, J. ; Lieberman, J. ; Martinvalet, Denis

In: Cell Death & Differentiation, 2015, vol. 22, no. 5, p. 862–874

Caspases and the cytotoxic lymphocyte protease granzyme B (GB) induce reactive oxygen species (ROS) formation, loss of transmembrane potential and mitochondrial outer membrane permeabilization (MOMP). Whether ROS are required for GB-mediated apoptosis and how GB induces ROS is unclear. Here, we found that GB induces cell death in an ROS-dependent manner, independently of caspases and MOMP. GB...