Mitochondria provide cells with energy to carry out fundamental organism functions. In addition to the synthesis of ATP, as an energy carrier, mitochondria are involved in such important phenomena as apoptosis, necrosis or aging. The proper functioning of mitochondria depends on the maintenance of transmembrane potential associated mainly with the difference in proton concentration across the inner mitochondrial membrane and ion transport and a number of substrates. One of the groups of proteins involved in ion transport are potassium channels of the inner mitochondrial membrane
Especially the increase in potassium ion transport across the inner mitochondrial membrane has aroused the interest of many researchers. It has been shown that the activation of mitochondrial potassium channels in various cell types can lead to cell protection against damage, a phenomenon known as cytoprotection.
Numerous studies have shown that the opening of potassium channels using chemicals called potassium channel activators can initiate processes that protect cells from damage caused by various factors, including hypoxia associated with cardiac arrest, ischemia. A full description of the mechanisms behind the phenomenon of cytoprotection induced by mitochondrial potassium channels, however, requires an understanding of their regulation, structure and interaction with other proteins.
REGULATION OF MITOCHONDRIAL ION CHANNELS BY INFRARED LIGHT
The beneficial effects of red or infrared light on the body in various situations associated with tissue damage has been observed for many years. It turns out that the main light absorber of this length is mitochondria, and in particular cytochrome oxidase, a protein that plays a key role in the generation of proton gradient in mitochondria. Our research indicates the possibility of regulating potassium channels by infrared light, as do the chemical compounds, potassium channel activators. Light induction of the phenomenon of cytoprotection in the heart muscle or the brain can have important implications in modern medicine. Our initial research suggests that mitochondrial potassium channels change their activity when exposed to infrared light.
FLAVONOIDS AS MITOCHONDRIAL POTASSIUM CHANNEL OPENERS
Mitochondrial potassium channels have been identified as fine regulators of mitochondrial function and, consequently, in the mechanisms underlying the cardioprotection. Interestingly, mitochondrial potassium channels represent a novel putative target for treating cardiovascular diseases, particularly myocardial infarction, and their modulators represent an interesting tool for pharmacological intervention. We took up the challenge of selecting flavonoids that show cardioprotective properties through the activation of mitochondrial potassium channels. Naringenin, quercetin and luteolin were demonstrated to be effective modulators of mitochondrial potassium channels activity.
MITOCHONDRIAL POTASSIUM CHANNELS IN CELLULAR SENESCENCE
A limited number of studies have shown functional changes in mitochondrial ion channels in aging and senescent cells. We have identified, for the first time, mitochondrial large-conductance calcium-regulated potassium channels in human smooth muscle mitochondria. This channel, with a conductance of 273 pS, was regulated by calcium ions and membrane potential. Additionally, it was activated by the potassium channel opener NS11021 and blocked by paxilline. Importantly, we have shown that senescence of these cells induced by hydrogen peroxide treatment leads to the disappearance of potassium channel protein levels and channel activity measured by the single channel patch-clamp technique. Our data suggest that disturbances in the expression of mitochondrial large conductance calcium-regulated potassium channels may be hallmarks of cellular senescence and contribute to the misregulation of mitochondrial function in senescent cells. [BARBARA]
POLYMER NANODISCS IN MITOCHONDRIAL POTASSIUM CHANNELS STUDIES
In the inner mitochondrial membrane, several potassium channels that play a role in cell life and death have been identified. One of these channels is the ATP-regulated potassium channel (mitoKATP). The ROMK2 potassium channel is a potential molecular component of the mitoKATP channel. The current study aimed to investigate the pharmacological modulation of the activity of the ROMK2 potassium channel expressed in Escherichia coli bacteria. ROMK2 was solubilized in polymer nanodiscs and incorporated in planar lipid bilayers. The impact of known mitoKATP channel modulators on the activity of the ROMK2 was characterized. We found that the ROMK2 channel was activated by the mitoKATP channel opener diazoxide and blocked by mitoKATP inhibitors such as ATP/Mg2+, 5-hydroxydecanoic acid, and antidiabetic sulfonylurea glibenclamide.
INTERACTION OF MITOCHONDRIAL POTASSIUM CHANNELS WITH INTRACELLULAR PROTEINS
It was found that activation of mitochondrial large conductance calcium activated potassium channel (mitoBKCa) preserves brain and heart muscle cells. In brain tumor cells, the respiratory chain modulates activity of the channel and might interact with the regulatory subunit of the mitoBKCa. Therefore the aim of the project is to characterize the regulation and interactions of mitoBKCa channel subunits with other
proteins. We also showed that the BK-VEDEC isoform of pore forming subunit of BKCa-type channel assembles in mitochondria to form a functional mitoBKCa channel. Revealing the regulation mechanisms and interactions between potassium channels of the inner mitochondrial membrane and other mitochondrial proteins (such as respiratory chain complexes) will help improve our understanding of cytoprotection mechanism induced by activation of mitochondrial potassium channels.
REGULATION OF MITOCHONDRIAL POTASSIUM CHANNELS WITH PARTICULATE MATTERS
Urban particulate matters (PM), a key component of air pollution, is a leading player of premature mortality and cardiopulmonary morbidity, associated with lung cancer, exacerbations of asthma and chronic pulmonary disease. Our data show that epithelial cells contain the functional the mitoK channels. However, the role of mitochondrial channels in epithelial cytoprotection is not known, especially in the context damage caused by urban PM or oxidative stress. We hypothesize that activation of the mitoK channels contribute to signaling pathway leading to cytoprotection of human epithelial cells upon damage caused by urban particulate matters.