Calcium & ROS: Two orchestra directors for the requiem of death. (January 2020) - SanMartín, Carol D.
Graphical abstract: Highlights: TNF triggers regulated necrosis of mycobacterium-infected macrophages. Mitochondrial reactive oxygen species (mitoROS) are produced in RIPK-1 and RIPK3-dependent way. mitoROS induces lysosomal enzymes activation that lead to BAX activation. BAX triggers ER ryanodine Ca +2 efflux from the endoplasmic reticulum into the mitochondrion. mitoROS and ER ryanodine Ca +2 efflux induces regulated necrosis. Abstract: Tumor necrosis factor alpha (TNF) triggers regulated necrosis of mycobacterium-infected macrophages through of mitochondrial reactive oxygen species (mitoROS) production in a RIPK1/3-dependent manner. To explain that, Roca and colleagues describe an inter-orgallenar circuit which involves the lysosomal ceramide production, mitoROS, BAX activation and RyR Ca 2+ efflux from the endoplasmic reticulum into the mitochondrion.