Περίληψη:
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 bioenergetic 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. (C) 2015 Elsevier Ltd. All rights reserved.
Συγγραφείς:
Bagkos, Georgios
Koufopoulos, Kostas
Piperi, Christina
