A non‐death function of the mitochondrial apoptosis apparatus in immunity

Abstract

Apoptosis is a frequent form of programmed cell death, but the apoptotic signaling pathway can also be engaged at a low level, in the absence of cell death. We here report that such sub‐lethal engagement of mitochondrial apoptosis signaling causes the secretion of cytokines from human epithelial cells in a process controlled by the Bcl‐2 family of proteins. We further show that sub‐lethal signaling of the mitochondrial apoptosis pathway is initiated by infections with all tested viral, bacterial, and protozoan pathogens and causes damage to the genomic DNA. Epithelial cells infected with these pathogens secreted cytokines, and this cytokine secretion upon microbial infection was substantially reduced if mitochondrial sub‐lethal apoptosis signaling was blocked. In the absence of mitochondrial pro‐apoptotic signaling, the ability of epithelial cells to restrict intracellular bacterial growth was impaired. Triggering of the mitochondrial apoptosis apparatus thus not only causes apoptosis but also has an independent role in immune defense.

Mitochondrial DNA in inflammation and immunity

“…However, we have found that under conditions of sub‐lethal stress, a limited number of mitochondria in a cell can undergo permeabilisation, called minority MOMP, leading to genomic instability and transformation . A recent report by Brokatsky et al reveals a link between pathogen invasion and activation of mitochondrial cell death machinery . In this study, it was found that various pathogens can induce limited mitochondrial permeabilisation.…”

Construction of homologous cancer cell membrane camouflage in a nano-drug delivery system for the treatment of lymphoma

“…In addition, classical apoptosis mainly encompasses the mitochondrial and death receptor pathways, of which the mitochondrial pathway is closely related to changes in intracellular mitochondrial transmembrane potential [60]. CCM@MSNs-ISOIM was found to reduce the intracellular mitochondrial transmembrane potential in NHL, and CCM@MSNs-ISOIM was also observed to significantly increase ROS levels in NHL, further suggesting that CCM@MSNs-ISOIM may induce apoptosis through the intracellular mitochondrial apoptosis pathway.…”

Construction of homologous cancer cell membrane camouflage in a nano-drug delivery system for the treatment of lymphoma

“…In addition, classical apoptosis mainly encompasses the mitochondrial and death receptor pathways, of which the mitochondrial pathway is closely related to changes in intracellular mitochondrial transmembrane potential [74]. CCM@MSNs-ISOIM was found to reduce the intracellular mitochondrial transmembrane potential in NHL, and CCM@MSNs-ISOIM was also observed to significantly increase ROS levels in NHL, further suggesting that CCM@MSNs-ISOIM may induce apoptosis through the intracellular mitochondrial apoptosis pathway.…”