Int Rev Cell Mol Biol. 2023 ;pii: S1937-6448(22)00136-8. [Epub ahead of print]374 83-127
Beyond the initial 'powerhouse' view, mitochondria have numerous functions in their mammalian cell and contribute to many physiological processes, and many of these we understand only partially. The control of apoptosis by mitochondria is firmly established. Many questions remain however how this function is embedded into physiology, and how other signaling pathways regulate mitochondrial apoptosis; the interplay of bacteria with the mitochondrial apoptosis pathway is one such example. The outer mitochondrial membrane regulates both import into mitochondria and the release of intermembrane, and in some situations also matrix components from mitochondria, and these mitochondrial components can have signaling function in the cytosol. One function is the induction of apoptotic cell death. An exciting, more recently discovered function is the regulation of inflammation. Mitochondrial molecules, both proteins and nucleic acids, have inflammatory activity when released from mitochondria, an activity whose regulation is intertwined with the activation of apoptotic caspases. Bacterial infection can have more general effects on mitochondrial apoptosis-regulation, through effects on host transcription and other pathways, such as signals controlled by pattern recognition. Some specialized bacteria have products that more specifically regulate signaling to the outer mitochondrial membrane, and to apoptosis; both pro- and anti-apoptotic mechanisms have been reported. Among the intriguing recent findings in this area are signaling contributions of porins and the sub-lethal release of intermembrane constituents. We will here review the literature and place the new developments into the established context of mitochondrial signaling during the contact of bacterial pathogens with human cells.
Keywords: Anti-apoptotic; Bacterial infection; Cytochrome c; Host cell; Immune response; Macrophage; Mitochondria; Outer mitochondrial membrane; Pro-apoptotic; Receptors; Second mitochondria-derived activator of caspase (Smac)