Membrane Potentials of Cancer Cells

Abstract

We discuss why the membrane potentials of cancer cells are often smaller than those of healthy cells, and why the stresses associated with reduced membrane potentials might not automatically cause destruction of cells by apoptosis.

The fact that cytochrome c appears as a key intermediary both in cellular respiration and in apoptosis suggests that damage to cytochrome c, or failure to express it, might reduce ion pumping across the cell membrane, thus diminishing the cellular membrane potential, whilst simultaneously damaging a key apoptosis pathway. Degraded respiration will also force the cell to obtain energy from glycolysis, consistent with the Warburg Hypothesis.

Deletion of functionality provided by mitochondria, such as respiration and apoptosis, would cause eukaryotic cells to behave in some ways like their distant ancestors, before they incorporated mitochondria.

The time that elapses between, on the one hand, the initial damage and reduction in membrane potential and, on the other hand, the onset of cancer allows a pre-emptive strike against misbehaving cells before they become cancerous. The modified electrical properties of impaired cells could function as targets for specially chosen or engineered species of immune system cells. E.g., it may be possible to decorate the surfaces of the damaged cells with molecules that first attach preferentially to cells with low membrane potentials, then attract and activate macrophages that will consume the errant cells and initiate a wider immune response. Immune cells that are attracted towards electrical targets, instead of relying entirely on structural motifs, are less likely to be affected by structural mutations of target cells.