Mitochondrial ion channels as oncological targets.
Mitochondria, the key bioenergetic intracellular organelles, harbor a number of proteins with proven or hypothetical ion channel functions. Growing evidence points to the important contribution of these channels to the regulation of mitochondrial function, such as ion homeostasis imbalances profoundly affecting energy transducing processes, reactive oxygen species production and mitochondrial integrity. Given the central role of mitochondria in apoptosis, their ion channels with the potential to compromise mitochondrial function have become promising targets for the treatment of malignancies. Importantly, in vivo evidence demonstrates the involvement of the proton-transporting uncoupling protein, a mitochondrial potassium channel, the outer membrane located porin and the permeability transition pore in tumor progression/control. In this review, we focus on mitochondrial channels that have been assigned a definite role in cell death regulation and possess clear oncological relevance. Overall, based on in vivo and in vitro genetic and pharmacological evidence, mitochondrial ion channels are emerging as promising targets for cancer treatment.
Department of Biology, University of Padova, Padova, Italy.
L
L
Leanza
CNR Institute of Neuroscience and Department of Biomedical Sciences, University of Padova, Padova, Italy.
M
M
Zoratti
Department of Molecular Biology, University of Duisburg-Essen, Essen, Germany.
E
E
Gulbins
Department of Biology, University of Padova, Padova, Italy.
I
I
Szabo
D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D016923:Cell Death; D006706:Homeostasis; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D010539:Permeability; D018272:Porins / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D017382:Reactive Oxygen Species; D000071256:Uncoupling Protein 1
D007473:Ion Channels; D024101:Mitochondrial Proteins; D018272:Porins; D015221:Potassium Channels; D017382:Reactive Oxygen Species; D000071256:Uncoupling Protein 1; D002118:Calcium