Point of No Return-What Is the Threshold of Mitochondria With Permeability Transition in Cells to Trigger Cell Death.

Programmed cell death (apoptosis) is essential part of the process of tissue regeneration that also plays role in the mechanism of pathology. The phenomenon of fast and transient permeability of mitochondrial membranes by various triggers, known as permeability transition pore (mPTP) leads to the release of proapoptotic proteins and acts as an initial step in initiation of apoptosis. However, a role for mPTP was also suggested for physiology and it is unclear if there is a threshold in number of mitochondria with mPTP which induces cell death and how this mechanism is regulated in different tissues.

Processes of Obtaining Nanostructured Materialswith a Hierarchical Porous Structure on the Example of Alginate Aerogels.

Currently, materials with specific, strictly defined functional properties are becoming increasingly important. A promising strategy for achieving these properties involves developing methods that facilitate the formation of hierarchical porous materials that combine micro-, meso-, and macropores in their structure. Macropores facilitate effective mass transfer of substances to the meso- and micropores, where further adsorption or reaction processes can occur.

Carbyne as a promising material for E-nose applications with machine learning.

There has been a lot of study and advancement in the area of carbon allotropes in the last several decades, driven by the exceptional and diverse physical and chemical characteristics of carbon nanomaterials. For example, nanostructured forms such as carbon nanotubes (CNTs), graphene, and carbon quantum dots have the potential to revolutionize various industries (Roston 2010; In and Noy 2014; Peng20147 1-29). The global scientific community continues to research in the field of creating new materials, particularly low-dimensional carbon allotropes such as CNTs and carbyne.

Depth-specific distribution of bacterial MAGs in permafrost active layer in Ny Ålesund, Svalbard (79°N).

Arctic soil microbial communities may shift with increasing temperatures and water availability from climate change. We examined temperature and volumetric liquid water content (VWC) in the upper 80 cm of permafrost-affected soil over 2 years (2018-2019) at the Bayelva monitoring station, Ny Ålesund, Svalbard. We show VWC increases with depth, whereas in situ temperature is more stable vertically, ranging from -5°C to 5 °C seasonally.

Interplay of mitochondrial calcium signalling and reactive oxygen species production in the brain.

Intracellular communication and regulation in brain cells is controlled by the ubiquitous Ca2+ and by redox signalling. Both of these independent signalling systems regulate most of the processes in cells including the cell surviving mechanism or cell death. In physiology Ca2+ can regulate and trigger reactive oxygen species (ROS) production by various enzymes and in mitochondria but ROS could also transmit redox signal to calcium levels via modification of calcium channels or phospholipase activity.

variants cause a phenotypic spectrum from early-onset Parkinson's disease to perinatal lethality by disrupting mitochondrial pathways.

Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here, we identify as a new gene implicated in PD and childhood neurodegeneration.

Energy substrate supplementation increases ATP levels and is protective to PD neurons.

Alteration of mitochondrial metabolism by various mutations or toxins leads to various neurological conditions. Age-related changes in energy metabolism could also play the role of a trigger for neurodegenerative disorders. Nonetheless, it is not clear if restoration of ATP production or supplementation of brain cells with substrates for energy production could be neuroprotective.

Mitochondrial Permeability Transition, Cell Death and Neurodegeneration.

Neurodegenerative diseases are chronic conditions occurring when neurons die in specific brain regions that lead to loss of movement or cognitive functions. Despite the progress in understanding the mechanisms of this pathology, currently no cure exists to treat these types of diseases: for some of them the only help is alleviating the associated symptoms. Mitochondrial dysfunction has been shown to be involved in the pathogenesis of most the neurodegenerative disorders.

Editor Profile: Andrey Abramov.

In this special interview series, we profile members of The FEBS Journal editorial board to highlight their research focus, perspectives on the journal and future directions in their field. Professor Andrey Abramov is a cell biologist and biophysicist at University College London's Queen Square Institute of Neurology. He has served as an Editorial Board Member of The FEBS Journal since 2015.

Cell-Permeable HSP70 Protects Neurons and Astrocytes Against Cell Death in the Rotenone-Induced and Familial Models of Parkinson's Disease.

Heat shock protein 70 (HSP70) is activated under stress response. Its involvement in cell protection, including energy metabolism and quality control makes it a promising pharmacological target. A strategy to increase HSP70 levels inside the cells is the application of recombinant HSP70.

RAGE induces physiological activation of NADPH oxidase in neurons and astrocytes and neuroprotection.

The transmembrane receptor for advanced glycation end products (RAGE) is a signaling receptor for many damage- and pathogen-associated molecules. Activation of RAGE is associated with inflammation and an increase in reactive oxygen species (ROS) production. Although several sources of ROS have been previously suggested, how RAGE induces ROS production is still unclear, considering the multiple targets of pathogen-associated molecules.

Detection of NADH and NADPH levels in vivo identifies shift of glucose metabolism in cancer to energy production.

Profound changes in the metabolism of cancer cells have been known for almost 100 years, and many aspects of these changes have continued to be actively studied and discussed. Differences in the results of various studies can be explained by the diversity of tumours, which have differing processes of energy metabolism, and by limitations in the methods used. Here, using fluorescence lifetime needle optical biopsy in a hepatocellular carcinoma (HCC) mouse model and patients with HCC, we measured reduced nicotinamide adenine dinucleotide (NADH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) in control liver, and in HCC tumours and their adjacent regions.

Titanium-Based Metasurfaces for Optoelectronics.

We report on the fabrication method that enables the development of transparent conductive metasurfaces capable of the resonant absorption of light in specific frequency bands. The approach is based on embedding linear sp-carbon chains and metallic nanoparticles in a porous matrix of titanium dioxide (TiO). We develop a blading technique for the formation of a periodical grating of TiO microtubes at the macroscale.

Astrocytes produce nitric oxide via nitrite reduction in mitochondria to regulate cerebral blood flow during brain hypoxia.

During hypoxia, increases in cerebral blood flow maintain brain oxygen delivery. Here, we describe a mechanism of brain oxygen sensing that mediates the dilation of intraparenchymal cerebral blood vessels in response to reductions in oxygen supply. In vitro and in vivo experiments conducted in rodent models show that during hypoxia, cortical astrocytes produce the potent vasodilator nitric oxide (NO) via nitrite reduction in mitochondria.

High levels of FAD autofluorescence indicate pathology preceding cell death.

Flavin adenine dinucleotide (FAD) autofluorescence from cells reports on the enzymatic activity which involves FAD as a cofactor. Most of the cellular FAD fluorescence comes from complex II of the electron transport chain in mitochondria and can be assessed with inhibitor analysis. The intensity of FAD autofluorescence is not homogeneous and vary between cells in tissue and in cell culture types.

Nrf2 depletion in the context of loss-of-function Keap1 leads to mitolysosome accumulation.

Transcription factor nuclear factor erythroid 2 p45-related factor 2 (Nrf2) is the principal determinant of the cellular redox homeostasis, contributing to mitochondrial function, integrity and bioenergetics. The main negative regulator of Nrf2 is Kelch-like ECH associated protein 1 (Keap1), a substrate adaptor for Cul3/Rbx1 ubiquitin ligase, which continuously targets Nrf2 for ubiquitination and proteasomal degradation. Loss-of-function mutations in Keap1 occur frequently in lung cancer, leading to constitutive Nrf2 activation.

Investigation of the 3D Printing Process Utilizing a Heterophase System.

Direct ink writing (DIW) requires careful selection of ink composition with specific rheological properties, and it has limitations, such as the inability to create overhanging parts or branched geometries. This study presents an investigation into enhancing the 3D printing process through the use of a heterophase system, aiming to overcome these limitations. A modification was carried out in the 3D printer construction, involving adjustments to the structural elements responsible for the extrusion device's movement.

Nrf2 regulates glucose uptake and metabolism in neurons and astrocytes.

The transcription factor Nrf2 and its repressor Keap1 mediate cell stress adaptation by inducing expression of genes regulating cellular detoxification, antioxidant defence and energy metabolism. Energy production and antioxidant defence employ NADH and NADPH respectively as essential metabolic cofactors; both are generated in distinct pathways of glucose metabolism, and both pathways are enhanced by Nrf2 activation. Here, we examined the role of Nrf2 on glucose distribution and the interrelation between NADH production in energy metabolism and NADPH homeostasis using glio-neuronal cultures isolated from wild-type, Nrf2-knockout and Keap1-knockdown mice.

HPRT1 Deficiency Induces Alteration of Mitochondrial Energy Metabolism in the Brain.

Alterations in function of hypoxanthine guanine phosphoribosyl transferase (HPRT), one of the major enzymes involved in purine nucleotide exchange, lead to overproduction of uric acid and produce various symptoms of Lesch-Nyhan syndrome (LNS). One of the hallmarks of LNS is maximal expression of HPRT in the central nervous system with the highest activity of this enzyme in the midbrain and basal ganglia. However, the nature of neurological symptoms has yet to be clarified in details.

Carbon monoxide neurotoxicity is triggered by oxidative stress induced by ROS production from three distinct cellular sources.

Carbon monoxide (CO) poisoning is one of the leading causes of toxic mortality and morbidity. We have studied the generation of reactive oxygen species in cortical neurons in culture in response to toxic doses of CO exposure. Fluorescence microscopy was used to measure the rate of free radical generation, lipid peroxidation, GSH level and also mitochondrial metabolism.

Nrf2 as a regulator of mitochondrial function: Energy metabolism and beyond.

Mitochondria are unique and essential organelles that mediate many vital cellular processes including energy metabolism and cell death. The transcription factor Nrf2 (NF-E2 p45-related factor 2) has emerged in the last few years as an important modulator of multiple aspects of mitochondrial function. Well-known for controlling cellular redox homeostasis, the cytoprotective effects of Nrf2 extend beyond its ability to regulate a diverse network of antioxidant and detoxification enzymes.