Targeting Mitochondria for Cancer Treatment – Two Types of Mitochondrial Dysfunction

Abstract

Two basic types of cancers were identified – those with the mitochondrial dysfunction in cancer cells (the Warburg effect) or in fibroblasts supplying energy rich metabolites to a cancer cell with functional mitochondria (the reverse Warburg effect). Inner membrane potential of the functional and dysfunctional mitochondria measured by fluorescent dyes (e.g. by Rhodamine 123) displays low and high values (apparent potential), respectively, which is in contrast to the level of oxidative metabolism. Mitochondrial dysfunction (full function) results in reduced (high) oxidative metabolism, low (high) real membrane potential, a simple layer (two layers) of transported protons around mitochondria, and high (low) damping of microtubule electric polar vibrations. Crucial modifications are caused by ordered water layer (exclusion zone). For the high oxidative metabolism one proton layer is at the mitochondrial membrane and the other at the outer rim of the ordered water layer. High and low damping of electric polar vibrations results in decreased and increased electromagnetic activity in cancer cells with the normal and the reverse Warburg effect, respectively. Due to nonlinear properties the electromagnetic frequency spectra of cancer cells and transformed fibroblasts are shifted in directions corresponding to their power deviations resulting in disturbances of interactions and escape from tissue control. The cancer cells and fibroblasts of the reverse Warburg effect tumors display frequency shifts in mutually opposite directions resulting in early generalization. High oxidative metabolism conditions high aggressiveness. Mitochondrial dysfunction, a gate to malignancy along the cancer transformation pathway, forms a narrow neck which could be convenient for cancer treatment.

ROCK1/Drp1-mediated aberrant mitochondrial fission is crucial for dopaminergic nerve cell apoptosis

“…2c, the content of ATP rapidly decreased in the MPP + -treated cells in a dose-dependent manner. The loss of mitochondrial membrane potential is also another indicator of mitochondrial dysfunction 25,26 . Therefore, we examined the mitochondrial membrane potential using JC-1 and rhodamine 123 staining.…”

Mitochondrial Dysfunction and Disturbed Coherence: Gate to Cancer

“…, the exclusion of positively and negatively charged entities is exchanged. The shift is confirmed by measurement of mitochondrial inner membrane potential by uptake and retention of positively charged fluorescent dyes and their high accumulation around dysfunctional mitochondria, which is overviewed and analysed in [ 59 ]. Damping of the electrodynamic oscillations might be caused by the mobile negatively charged entities (electrons) at the upper boundary of the exclusion layer.…”

“…Mitochondria in fibroblasts associated with cancer cells are dysfunctional and energy-rich metabolites such as lactate, pyruvate, glutamine, keton beta-hydroxybutyrate (BHB) are supplied from fibroblasts to cancer cells with fully functional mitochondria. The main characteristics of the reverse Warburg effect in cancers have been previously addressed in detail [ 59 ].…”

Role and mechanism of mitochondrial deoxyguanosine kinase in lung cancer tumorigenesis

“…DGUOK是定位于线粒体中负责嘌呤脱氧核苷酸 补救合成途径的限速酶 [10] , 为了进一步解析DGUOK 线粒体功能对肿瘤的发生发展起着重要的调控作 用 [11,12] . Deletion or mutation of mitochondrial deoxyguanosine kinase (dguok) is a major cause of mitochondrial DNA deletion syndrome.…”