Chlamydia trachomatis Plasmid-Encoded Protein pORF5 Induces Mitochondrial Fission by Activating Drp1 via the MAPK/ERK Signaling Pathway.

Chlamydia trachomatis (C. trachomatis) is a strictly parasitic pathogen that heavily relies on host cells for generating energy, acquiring nutrients, and evading immune responses. Mitochondrial dynamics-the balance of fusion and fission-are integral to cellular functions, including the maintenance of homeostasis, the regulation of metabolic processes, and the modulation of host innate immune pathways. Accordingly, C. trachomatis can specifically change the host mitochondrial dynamics to promote its intracellular replication. Mitochondrial fragmentation has been observed during the later phases of C. trachomatis infection; Nevertheless, the exact mechanisms remain poorly defined. The research aimed to determine the effect of the C. trachomatis secretory protein pORF5 in this process. In stable pORF5-expressing Hela cells, we employed confocal microscopy to analyze mitochondrial morphology and Western blotting to measure the expression of key mitochondrial dynamics proteins. Finally, immunofluorescence was used to monitor Drp1 mitochondrial translocation, and the effects of a pathway inhibitor on mitochondrial fission were evaluated. We observed that the plasmid-encoded protein pORF5 can induce mitochondrial fission. Mechanistically, this process is dependent on the activation of the ERK/Drp1 signaling axis, which indicates the crucial importance of this pathway and its effect on pORF5-induced mitochondrial fragmentation.