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Best posted an update 12 months ago
re, recommendations for future research are proposed.Organisms living in high altitude must adapt to environmental conditions with hypoxia and low temperature, e.g. by changes in the structure and function of proteins associated with oxidative phosphorylation in mitochondria. Here we analysed the signs of adaptive evolution in 27 mitogenomes of endemic Ethiopian rats (Stenocephalemys), where individual species adapted to different elevation. Significant signals of positive selection were detected in 10 of the 13 mitochondrial protein-coding genes, with a majority of functional substitutions in the NADH dehydrogenase complex. Higher frequency of positively selected sites was found in phylogenetic lineages corresponding to Afroalpine specialists.Endothelial mitochondria play important signaling roles critical for the regulation of various cellular processes, including calcium signaling, ROS generation, NO synthesis or inflammatory response. Mitochondrial stress or disturbances in mitochondrial function may participate in the development and/or progression of endothelial dysfunction and could precede vascular diseases. Vascular functions are also strictly regulated by properly functioning degradation machinery, including autophagy and mitophagy, and tightly coordinated by mitochondrial and endoplasmic reticulum responses to stress. Within this review, current knowledge related to the development of cardiovascular disorders and the importance of mitochondria, endoplasmic reticulum and degradation mechanisms in vascular endothelial functions are summarized.The puzzling traits related to the evolutionary aspect of mitochondria, still positions the mitochondrion at the center of the research. The theory of endosymbiosis popularized by Lynn Margulis in 1967 gained prominence wherein the mitochondrion is believed to have emerged as a prokaryote and later integrated into the eukaryotic system. This semi-autonomous organelle has bagged two responsible but perilous cellular functions a) energy metabolism, and b) calcium buffering, though both are interdependent. While most of the mitochondrial functions are saliently regulated by calcium ions, the calcium buffering role of mitochondria decides the cellular fate. Though calcium overload in few mitochondria makes them dysfunctional at the early stage of cellular stress, this doesn’t lead to sudden cell death due to critical checkpoints like mitophagy, mitochondrial fusion, etc. see more Thus, mitochondrion juggles with multiple crucial cellular functions with its calcium buffering skill.Protein phosphorylation is one of the best-known post-translational modifications occurring in all domains of life. In eukaryotes, protein phosphorylation affects all cellular compartments including mitochondria. High-throughput techniques of mass spectrometry combined with cell fractionation and biochemical methods yielded thousands of phospho-sites on hundreds of mitochondrial proteins. We have compiled the information on mitochondrial protein kinases and phosphatases and their substrates in Saccharomyces cerevisiae and provide the current state-of-the-art overview of mitochondrial protein phosphorylation in this model eukaryote. Using several examples, we describe emerging features of the yeast mitochondrial phosphoproteome and present challenges lying ahead in this exciting field.Individuals with Down syndrome (DS) have an extra copy of chromosome 21. Clinical observations and preclinical studies both suggest that DS is associated with altered bioenergetic pathways. Several studies have reported that differentially expressed genes in DS are located not only on chromosome 21 but also on all other chromosomes. Numerous sets of microarray and RNA-seq data are publicly accessible through the Gene Expression Omnibus. We have conducted a meta-analysis on differentially expressed genes between DS and control subjects. Data deposited before July 1, 2020, were identified by using the search terms “Down syndrome” or “trisomy 21” and “human”. Gene expression data were analyzed and normalized for each study. The mixed effect model was used to identify the differentially expressed genes. We conclude that in DS more than 60% of the genes located on chromosome 21 are significantly upregulated and none of them are downregulated. In addition, a significant dysregulation of genes occurs on all other chromosomes as well. Several of the upregulated genes in DS encode for important components of various bioenergetic pathways, for instance PFKL and ACLY. Genes involved in oxidative phosphorylation are mostly downregulated in DS. The gene expression alterations are consistent with the development of significant metabolic disturbances (“pseudohypoxia”) in DS cells, which may explain some of the well-known functional defects (ranging from neuronal dysfunction to reduced exercise tolerance) associated with DS.C-Src kinase is localized in several subcellular compartments, including mitochondria where it is involved in the regulation of organelle functions and overall metabolism. Surprisingly, the characterization of the intramitochondrial Src interactome has never been fully determined. Using in vitro proximity-dependent biotin identification (BioID) coupled to mass spectrometry, we identified 51 candidate proteins that may interact directly or indirectly with c-Src within the mitochondrial matrix. Pathway analysis suggests that these proteins are involved in a large array of mitochondrial functions such as protein folding and import, mitochondrial organization and transport, oxidative phosphorylation, tricarboxylic acid cycle and metabolism of amino and fatty acids. Among these proteins, we identified 24 tyrosine phosphorylation sites in 17 mitochondrial proteins (AKAP1, VDAC1, VDAC2, VDAC3, LonP1, Hsp90, SLP2, PHB2, MIC60, UBA1, EF-Tu, LRPPRC, ACO2, OAT, ACAT1, ETFβ and ATP5β) as potential substrates for intramitochondrial Src using in silico prediction of tyrosine phospho-sites. Interaction of c-Src with SLP2 and ATP5β was confirmed using coimmunoprecipitation. This study suggests that the intramitochondrial Src could target several proteins and regulate different mitochondrial functions.