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Cell Physiol Biochem. 2019;53(S1):11-43. doi: 10.33594/000000192.

Small-Molecule Modulators of Mitochondrial Channels as Chemotherapeutic Agents.

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Dept. of Biomedical Sciences, University of Padova, Padova, Italy.
Dept. of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
CNR Neuroscience Institute, Padova, Italy.
Dept. of Biomedical Sciences, University of Padova, Padova, Italy,


Ion channels residing in the inner (IMM) and outer (OMM) mitochondrial membranes are emerging as noteworthy pharmacological targets in oncology. While these aspects have not been investigated for all of them, a role in cancer growth and/or metastasis and/or drug resistance has been shown at least for the IMM-residing Ca2+ uniporter complex and K+- selective mtKV1.3, mtIKCa, mtSKCa and mtTASK-3, and for the OMM Voltage-Dependent Anion Channel (mitochondrial porin). A special case is that of the Mitochondrial Permeability Transition Pore, a large pore which forms in the IMM of severely stressed cells, and which may be exploited to precipitate the death of cancerous cells. Here we briefly discuss the oncological relevance of mitochondria and their channels, and summarize the methods that can be adopted to selectively target these intracellular organelles. We then present an updated list of known mitochondrial channels, and review the pharmacology of those with proven relevance for cancer.


Mitochondrial channels; Cancer; Channel modulators; Mitochondria-targeting

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