Mitochondrial emitted electromagnetic signals mediate retrograde signaling

• Published in: Medical hypotheses Vol. 85; no. 6; pp. 810 - 818
• Main Authors: Bagkos, Georgios, Koufopoulos, Kostas, Piperi, Christina
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.12.2015
• Subjects: Animals; Cell Nucleus - physiology; Electromagnetic Fields; Gene Expression Regulation - physiology; Humans; Internal Medicine; Membrane Potential, Mitochondrial - physiology; Mitochondria - physiology; Mitochondrial Membranes - physiology; Models, Biological; Signal Transduction - physiology
• ISSN: 0306-9877; 1532-2777
• DOI: 10.1016/j.mehy.2015.10.004

Abstract Recent evidence shows that mitochondria regulate nuclear transcriptional activity both in normal and cell stress conditions, known as retrograde signaling. Under normal mitochondrial function, retrograde signaling is associated with mitochondrial biogenesis, normal cell phenotype and metabolic profile. In contrast, mitochondrial dysfunction leads to abnormal (oncogenic) cell phenotype and altered bio-energetic profile (nucleus reprogramming). Despite intense research efforts, a concrete mechanism through which mitochondria determine the group of genes expressed by the nucleus is still missing. The present paper proposes a novel hypothesis regarding retrograde signaling. More specifically, it reveals the mitochondrial membrane potential (MMP) and the accompanied strong electromagnetic field (EF) as key regulatory factors of nuclear activity. Mitochondrial emitted EFs extend in long distance and affect the function of nuclear membrane receptors. Depending on their frequencies, EFs can directly activate or deactivate different groups of nuclear receptors and so determine nuclear gene expression. One of the key features of the above hypothesis is that nuclear membrane receptors, besides their own endogenous or chemical ligands (hormones, lipids, etc.), can also be activated by electromagnetic signals. Moreover, normal MMP values (about −140 mV) are associated with the production of high ATP quantities and small levels of reactive oxygen species (ROS) while the hyperpolarization observed in all cancer cell types leads to a dramatic fall in ATP production and an analogous increase in ROS. The diminished ATP and increased ROS production negatively affect the function of all cellular systems including nucleus. Restoration of mitochondrial function, which is characterized by the fluctuation of MMP and EF values within a certain (normal) range, is proposed as a necessary condition for normal nuclear function and cancer therapy.