Granzyme F (GZMF)

Granzyme F (GzmF) belongs to a unique group of granzymes in mice. Murine GzmF is highly expressed in NK3.1 cells and in lymphokine-activated killer (LAK) cells. However, the manner in which GzmF works in granule-mediated cytolysis is unknown. GzmF causes a novel cell death pathway. GzmF-induced chromatin was incompletely condensed and segmented at the nuclear periphery. Cellular organelles were damaged and the cytoplasm showed an extensive vacuolization that is reminiscent of necroptosis. GzmF can cause rapid mitochondrial swelling, depolarization and reactive oxygen species accumulation. GzmF-induced death does not involve caspase activation, Bid cleavage or activation of DNA nickase NM23H1. GzmF-silenced LAK cells showed reduced cytotoxicity against caspase-inhibited target tumor cells.