The oxidative phosphorylation system1 in mammalian mitochondria plays a key role in transducing energy from ingested nutrients2. Mitochondrial metabolism is dynamic and can be reprogrammed to support both catabolic and anabolic reactions, depending on physiological demands or disease states. Rewiring of mitochondrial metabolism is intricately linked to metabolic diseases and promotes tumour growth3–5. Here, we demonstrate that oral treatment with an inhibitor of mitochondrial transcription (IMT)6 shifts whole-animal metabolism towards fatty acid oxidation, which, in turn, leads to rapid normalization of body weight, reversal of hepatosteatosis and restoration of normal glucose tolerance in male mice on a high-fat diet. Paradoxically, the IMT treatment causes a severe reduction of oxidative phosphorylation capacity concomitant with marked upregulation of fatty acid oxidation in the liver, as determined by proteomics and metabolomics analyses. The IMT treatment leads to a marked reduction of complex I, the main dehydrogenase feeding electrons into the ubiquinone (Q) pool, whereas the levels of electron transfer flavoprotein dehydrogenase and other dehydrogenases connected to the Q pool are increased. This rewiring of metabolism caused by reduced mtDNA expression in the liver provides a principle for drug treatment of obesity and obesity-related pathology.
This work is devoted to unbuffered and buffered water treatment by means of atmospheric pressure cold plasma of electrical discharges. The interest in the activation of these two liquids by plasma-induced, gaseous-phase chemistry ranges over a wide area of potential applications and interdisciplinary scientific fields. These include biology, medicine, sanitation, environmental restoration, agriculture, etc. Atmospheric pressure cold plasma is here produced in the form of a plasma jet and set into physical contact with the liquid specimens. The operational window of the treatment, in terms of plasma reactivity, is determined by means of UV-NIR optical emission spectroscopy, and the treated liquids are probed in a variety of respects. Evaporation rate, temperature, acidity and basicity, resistivity, and oxidation-reduction potential are measured as a function of the treatment time, either in-situ or ex-situ. The formation of principal reactive oxygen species, i.e., •OH, H2O2 and , with a plasma jet mean power lower than 400 mW, is eventually demonstrated and their concentration is measured with original methods borrowed from the biology field. The experimental results are linked to reports published over the last ten years, which are compiled in a brief but meaningful review.
Mammalian mitochondrial DNA (mtDNA) inheritance differs fundamentally from nuclear inheritance owing to exclusive maternal transmission, high mutation rate, and lack of recombination. Two key mechanisms shape this inheritance: the bottleneck, which drives stochastic transmission of maternal mtDNA variants, and purifying selection, which actively removes mutant mtDNA. Whether these mechanisms interact has been unresolved. To address this question, we generated a series of mouse models with random mtDNA mutations alongside alleles altering mtDNA copy number or decreasing autophagy. We demonstrate that tightening the mtDNA bottleneck increases heteroplasmic variance between individuals, causing lower mutational burden and nonsynonymous-to-synonymous ratios. In contrast, reduced autophagy weakens purifying selection, leading to decreased interoffspring heteroplasmic variance and increased mutational burden with higher nonsynonymous-to-synonymous ratios. These findings provide experimental evidence that the mtDNA bottleneck size modulates the efficacy of purifying selection. Our findings yield fundamental insights into the processes governing mammalian mtDNA transmission with direct implications for the origin and propagation of mtDNA mutations causing human disease.
The critical arguments for radiofrequency radiation exposure limits are currently based on the principle that radio frequencies (RF) and electromagnetic fields (EMFs) are non-ionising, and their exposure limits are even 100-fold lower than those emitted from the Sun in the whole RF-EMF spectrum. Nonetheless, this argument has been challenged by numerous experimental and theoretical studies on the diverse biological effects of RF-EMF at much lower power density (W/m2) levels than today’s exposing limits. On the other hand, less attention has been given to counterarguments based on the differences in the physics concepts underlying man-made versus natural electromagnetic radiation (EMR) and on the fact that man’s biology has been adapted to the natural EMR levels reaching Earth’s surface at single EMF wavelengths, which are the natural limits of man’s exposure to EMFs. The article highlights the main points of interaction of natural and man-made radiation with biomatter and reveals the physical theoretical background that explains the effects of man-made microwave radiation on biological matter. Moreover, the article extends its analysis on experimental quantum effects, establishing the “ionising-like” effects of man-made microwave radiation on biological matter.
1 February 2022 in Archives of Biochemistry and Biophysics