| Autor: |
Holland RL; Department of Pathobiology, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, Illinois, 61801., Bosi KD; Department of Microbiology, School of Molecular and Cellular Biology, University of Illinois Urbana-Champaign, Urbana, Illinois, 61801., Seeger AY; Department of Microbiology, School of Molecular and Cellular Biology, University of Illinois Urbana-Champaign, Urbana, Illinois, 61801., Blanke SR; Department of Pathobiology, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, Illinois, 61801.; Department of Microbiology, School of Molecular and Cellular Biology, University of Illinois Urbana-Champaign, Urbana, Illinois, 61801.; Biomedical and Translational Sciences Department, Carle Illinois College of Medicine, University of Illinois, Urbana, Illinois 61801. |
| Abstrakt: |
The Helicobacter pylori vacuolating cytotoxin (VacA) is an intracellular, mitochondrial-targeting exotoxin that rapidly causes mitochondrial dysfunction and fragmentation. Although VacA targeting of mitochondria has been reported to alter overall cellular metabolism, there is little known about the consequences of extended exposure to the toxin. Here, we describe studies to address this gap in knowledge, which have revealed that mitochondrial dysfunction and fragmentation are followed by a time-dependent recovery of mitochondrial structure, mitochondrial transmembrane potential, and cellular ATP levels. Cells exposed to VacA also initially demonstrated a reduction in oxidative phosphorylation, as well as increase in compensatory aerobic glycolysis. These metabolic alterations were reversed in cells with limited toxin exposure, congruent with the recovery of mitochondrial transmembrane potential and the absence of cytochrome c release from the mitochondria. Taken together, these results are consistent with a model that mitochondrial structure and function are restored in VacA-intoxicated cells. |
