Perturbed mitochondrial dynamics, an emerging aspect of epithelial-microbe interactions.

Mitochondria exist in a complex network that is constantly remodeling via the processes of fission and fusion in response to intracellular conditions and extracellular stimuli. Excessive fragmentation of the mitochondrial network, as a consequence of an imbalance between fission and fusion, reduces the cells' capacity to generate ATP and can be a forerunner of cytotoxicity and subsequent cell death. Given the critical roles mitochondria play in cellular homeostasis and innate immunity, it is not surprising that many bacterial pathogens can disrupt mitochondrial activity. Here we review data showing that infection with bacterial pathogens (as well as viruses) can alter the balance between mitochondrial fragmentation and fusion, preventing normal remodeling (i.e. dynamics) and can lead to cell death. Current data indicate that infection of epithelia (or macrophages) with microbial pathogens will ultimately result in excessive fragmentation of the mitochondrial network. Concerted research efforts are required to elucidate fully the processes that regulate mitochondrial dynamics, the mechanisms by which microbes affect epithelial mitochondrial fission and/or fusion and the implications of this for susceptibility to infectious disease. We speculate that the commensal microbiome of the gut may be important for normal epithelial mitochondrial form and function. Drugs designed to counteract the effect of microbial pathogen interference with mitochondrial dynamics may be a new approach to infectious disease at mucosal surfaces.