Contribution of Mitochondrial Ion Channels to Chemo-Resistance in Cancer Cells

Abstract

Mitochondrial ion channels are emerging oncological targets, as modulation of these ion-transporting proteins may impact on mitochondrial membrane potential, efficiency of oxidative phosphorylation and reactive oxygen production. In turn, these factors affect the release of cytochrome c, which is the point of no return during mitochondrial apoptosis. Many of the currently used chemotherapeutics induce programmed cell death causing damage to DNA and subsequent activation of p53-dependent pathways that finally leads to cytochrome c release from the mitochondrial inter-membrane space. The view is emerging, as summarized in the present review, that ion channels located in this organelle may account in several cases for the resistance that cancer cells can develop against classical chemotherapeutics, by preventing drug-induced apoptosis. Thus, pharmacological modulation of these channel activities might be beneficial to fight chemo-resistance of different types of cancer cells.

Revisiting Mitochondria Scored Cancer Progression and Metastasis

“…ROS in turn may activate MPTP or the caspase-independent ROS-triggered parthanatos (poly (ADP-ribose) polymerase-1 dependent cell death). In addition, MPTP can also be triggered by Ca2+overload in the mitochondrial matrix or by IMM depolarization and by several other factors (for example oxidative stress) [ 65 ].…”

Intracellular monitoring of NADH release from mitochondria using a single functionalized nanowire electrode

“…4b, curve 2), which suggested that RSV may specically induce mPTP opening and NADH release in cancer cells. [62][63][64] This is a very exciting result but the underlying mechanism needs to be deeply investigated.…”

Mitochondrial Ion Channels of the Inner Membrane and Their Regulation in Cell Death Signaling

“…Many recent reviews describe the role of mitochondrial ion channels in cell death, especially in apoptosis and necrosis ( Biasutto et al, 2016 ; Krabbendam et al, 2018 ; Magri et al, 2018 ; Szewczyk et al, 2018 ; Peruzzo and Szabo, 2019 ). In this minireview, we provide an updated overview specifically on the link between the complex regulation of the IMM channels and death induction, with special attention given to the permeability transition pore (PTP) and the mitochondrial calcium uniporter, two master regulators of cell fate.…”