Small-Molecule Modulators of Mitochondrial Channels as Chemotherapeutic Agents.

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.

Parrasia S ，Mattarei A ，Furlan A ，Zoratti M ，Biasutto L ... -  《-》

Mitochondrial ion channels as therapeutic targets.

The study of mitochondrial ion channels changed our perception of these double-wrapped organelles from being just the power house of a cell to the guardian of a cell's fate. Mitochondria communicate with the cell through these special channels. Most of the time, the message is encoded by ion flow across the mitochondrial outer and inner membranes. Potassium, sodium, calcium, protons, nucleotides, and proteins traverse the mitochondrial membranes in an exquisitely regulated manner to control a myriad of processes, from respiration and mitochondrial morphology to cell proliferation and cell death. This review is an update on both well established and putative mitochondrial channels regarding their composition, function, regulation, and therapeutic potential.

Peixoto PM ，Ryu SY ，Kinnally KW 《-》

Mitochondrial ion channels as oncological targets.

Leanza L ，Zoratti M ，Gulbins E ，Szabo I ... -  《-》

Mitochondrial ion channels/transporters as sensors and regulators of cellular redox signaling.

O-Uchi J ，Ryu SY ，Jhun BS ，Hurst S ，Sheu SS ... -  《-》

Complex formation and turnover of mitochondrial transporters and ion channels.

McStay GP 《-》