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Regulation of Mitochondrial Permeability Transition Pore Opening by Monovalent Cations in Liver Mitochondria
The opening of the permeability transition pore (PTP) in mitochondria is a key event in the initiation of cell death in various pathologic states, including ischemia/reperfusion. The activation of K(+) transport into mitochondria protects cells from ischemia/reperfusion. However, the role of K(+) tr...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252971/ https://www.ncbi.nlm.nih.gov/pubmed/37298189 http://dx.doi.org/10.3390/ijms24119237 |
Sumario: | The opening of the permeability transition pore (PTP) in mitochondria is a key event in the initiation of cell death in various pathologic states, including ischemia/reperfusion. The activation of K(+) transport into mitochondria protects cells from ischemia/reperfusion. However, the role of K(+) transport in PTP regulation is unclear. Here, we studied the role of K(+) and other monovalent cations in the regulation of the PTP opening in an in vitro model. The registration of the PTP opening, membrane potential, Ca(2+)-retention capacity, matrix pH, and K(+) transport was performed using standard spectral and electrode techniques. We found that the presence of all cations tested in the medium (K(+), Na(+), choline(+), and Li(+)) strongly stimulated the PTP opening compared with sucrose. Several possible reasons for this were examined: the effect of ionic strength, the influx of cations through selective and non-selective channels and exchangers, the suppression of Ca(2+)/H(+) exchange, and the influx of anions. The data obtained indicate that the mechanism of PTP stimulation by cations includes the suppression of K(+)/H(+) exchange and acidification of the matrix, which facilitates the influx of phosphate. Thus, the K(+)/H(+) exchanger and the phosphate carrier together with selective K(+) channels compose a PTP regulatory triad, which might operate in vivo. |
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