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Mitochondria are key players of cellular metabolism, Ca2+ homeostasis, and apoptosis. The functionality of mitochondria is tightly regulated, and dysfunctional mitochondria are removed via mitophagy, a specialized form of autophagy that is compromised in hereditary forms of Parkinson's disease. Through mitophagy, cells are able to cope with mitochondrial stress until the damage becomes too great, which leads to the activation of pro-apoptotic BCL-2 family proteins located on the outer mitochondrial membrane. Active pro-apoptotic BCL-2 proteins facilitate the release of cytochrome c from the mitochondrial intermembrane space (IMS) into the cytosol, committing the cell to apoptosis by activating a cascade of cysteinyl-aspartate specific proteases (caspases). We are only beginning to understand how the choice between mitophagy and the activation of caspases is determined on the mitochondrial surface. Intriguingly in neurons, caspase activation also plays a non-apoptotic role in synaptic plasticity. Here we review the current knowledge on the interplay between mitophagy and caspase activation with a special focus on the central nervous system.Cyanobacteria are ubiquitous oxygenic photosynthetic bacteria with a versatile metabolism that is highly dependent on effective protein targeting. Protein sorting in diderm bacteria is not trivial and, in cyanobacteria, even less so due to the presence of a complex membrane system the outer membrane, the plasma membrane and the thylakoid membrane. In cyanobacteria, protein import into the thylakoids is essential for photosynthesis, export to the periplasm fulfills a multifunctional role in maintaining cell homeostasis, and secretion mediates motility, DNA uptake and environmental interactions. Intriguingly, only one set of genes for the general secretory and the twin-arginine translocation pathways seem to be present. However, these systems have to operate in both plasma and thylakoid membranes. This raises the question of how substrates are recognized and targeted to their correct, final destination. Additional complexities arise when a protein has to be secreted across the outer membrane, where very little is known regarding the mechanisms involved. Given their ecological importance and biotechnological interest, a better understanding of protein targeting in cyanobacteria is of great value. This review will provide insights into the known knowns of protein targeting, propose hypotheses based on available genomic sequences and discuss future directions.Deoxyribozymes (DNAzymes) are single-stranded DNA molecules that catalyze a broad range of chemical reactions. The 10-23 DNAzyme catalyzes the cleavage of RNA strands and can be designed to cleave essentially any target RNA, which makes it particularly interesting for therapeutic and biosensing applications. The activity of this DNAzyme in vitro is considerably higher than in cells, which was suggested to be a result of the low intracellular concentration of bioavailable divalent cations. While the interaction of the 10-23 DNAzyme with divalent metal ions was studied extensively, the influence of monovalent metal ions on its activity remains poorly understood. Here, we characterize the influence of monovalent and divalent cations on the 10-23 DNAzyme utilizing functional and biophysical techniques. Our results show that Na+ and K+ affect the binding of divalent metal ions to the DNAzymeRNA complex and considerably modulate the reaction rates of RNA cleavage. We observe an opposite effect of high levels of Na+ and K+ concentrations on Mg2+- and Mn2+-induced reactions, revealing a different interplay of these metals in catalysis. Based on these findings, we propose a model for the interaction of metal ions with the DNAzymeRNA complex.Fatty acids (FAs) are a highly diverse class of molecules that can have variable chain length, number of double bonds and hydroxylation sites. FAs with 22 or more carbon atoms are described as very long chain fatty acids (VLCFAs). VLCFAs are synthesized in the endoplasmic reticulum (ER) through a four-step elongation cycle by membrane embedded enzymes. VLCFAs are precursors for the synthesis of sphingolipids (SLs) and glycerophospholipids. Besides their role as lipid constituents, VLCFAs are also found as precursors of lipid mediators. Mis-regulation of VLCFA metabolism can result in a variety of inherited diseases ranging from ichthyosis, to myopathies and demyelination. The enzymes for VLCFA biosynthesis are evolutionary conserved and many of the pioneering studies were performed in the model organism Saccharomyces cerevisiae. D-Cycloserine A growing body of evidence suggests that VLCFA metabolism is intricately regulated to maintain lipid homeostasis. In this review we will describe the metabolism of VLCFAs, how they are synthesized, transported and degraded and how these processes are regulated, focusing on budding yeast. We will review how lipid metabolism and membrane properties are affected by VLCFAs and which impact mutations in the biosynthetic genes have on physiology. We will also briefly describe diseases caused by mis-regulation of VLCFAs in human cells.The worldwide spread of coronavirus disease 2019 (COVID-19) has generated a global health crisis and more than a million deaths so far. Epidemiological and clinical characteristics of COVID-19 are increasingly reported, along with its potential relationship with overweight and/or obesity. Therefore, we aim here to review the current scientific literature on the impact of overweight and/or obesity among hospitalized patients who have developed severe or critical forms of COVID-19. Following PRISMA guidelines, our literature search identified over 300 scientific articles using the keywords "obesity" and "COVID-19", 22 of which were finally selected for reporting useful information on the association between overweight/obesity and disease severity. In particular, in 11 out of the 14 studies (79%) which evaluated the association between obesity and disease severity providing also a risk estimate (i.e., the odd ratio; OR), the OR value was constantly >2. Although the studies were found to be heterogeneous in terms of design, population, sample size and endpoints, in most cases a significant association was found between obesity and the risk of progressing to severe COVID-19 illness, intensive care unit admission and/or death.
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