ResearchPad - organelles-localization https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[MicroRNAs and long non-coding RNAs as novel regulators of ribosome biogenesis]]> https://www.researchpad.co/article/elastic_article_10897 Ribosome biogenesis is the fine-tuned, essential process that generates mature ribosomal subunits and ultimately enables all protein synthesis within a cell. Novel regulators of ribosome biogenesis continue to be discovered in higher eukaryotes. While many known regulatory factors are proteins or small nucleolar ribonucleoproteins, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) are emerging as a novel modulatory layer controlling ribosome production. Here, we summarize work uncovering non-coding RNAs (ncRNAs) as novel regulators of ribosome biogenesis and highlight their links to diseases of defective ribosome biogenesis. It is still unclear how many miRNAs or lncRNAs are involved in phenotypic or pathological disease outcomes caused by impaired ribosome production, as in the ribosomopathies, or by increased ribosome production, as in cancer. In time, we hypothesize that many more ncRNA regulators of ribosome biogenesis will be discovered, which will be followed by an effort to establish connections between disease pathologies and the molecular mechanisms of this additional layer of ribosome biogenesis control.

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<![CDATA[The road to the structure of the mitochondrial respiratory chain supercomplex]]> https://www.researchpad.co/article/elastic_article_9190 The four complexes of the mitochondrial respiratory chain are critical for ATP production in most eukaryotic cells. Structural characterisation of these complexes has been critical for understanding the mechanisms underpinning their function. The three proton-pumping complexes, Complexes I, III and IV associate to form stable supercomplexes or respirasomes, the most abundant form containing 80 subunits in mammals. Multiple functions have been proposed for the supercomplexes, including enhancing the diffusion of electron carriers, providing stability for the complexes and protection against reactive oxygen species. Although high-resolution structures for Complexes III and IV were determined by X-ray crystallography in the 1990s, the size of Complex I and the supercomplexes necessitated advances in sample preparation and the development of cryo-electron microscopy techniques. We now enjoy structures for these beautiful complexes isolated from multiple organisms and in multiple states and together they provide important insights into respiratory chain function and the role of the supercomplex. While we as non-structural biologists use these structures for interpreting our own functional data, we need to remind ourselves that they stand on the shoulders of a large body of previous structural studies, many of which are still appropriate for use in understanding our results. In this mini-review, we discuss the history of respiratory chain structural biology studies leading to the structures of the mammalian supercomplexes and beyond.

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<![CDATA[Immunohistochemical staining reveals differential expression of ACSL3 and ACSL4 in hepatocellular carcinoma and hepatic gastrointestinal metastases]]> https://www.researchpad.co/article/N00eda29b-3a72-4a58-833e-b43beac904cf Long-chain fatty acyl CoA synthetases (ACSLs) activate fatty acids by CoA addition thus facilitating their intracellular metabolism. Dysregulated ACSL expression features in several cancers and can affect processes such as ferroptosis, fatty acid β-oxidation, prostaglandin biosynthesis, steroidogenesis and phospholipid acyl chain remodelling. Here we investigate long chain acyl-CoA synthetase 3 (ACSL3) and long chain acyl-CoA synthetase 4 (ACSL4) expression in liver malignancies. The expression and subcellular localisations of the ACSL3 and ACSL4 isoforms in hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA) and hepatic metastases were assessed by immunohistochemical analyses of multiple tumour tissue arrays and by subcellular fractionation of cultured HepG2 cells. The expression of both enzymes was increased in HCC compared with normal liver. Expression of ACSL3 was similar in HCC and hepatic metastases but lower in healthy tissue. Increased ACSL3 expression distinguished HCC from CCA with a sensitivity of 87.2% and a specificity of 75%. ACSL4 expression was significantly greater in HCC than in all other tumours and distinguished HCC from normal liver tissue with a sensitivity of 93.8% and specificity of 93.6%. Combined ACSL3 and ACSL4 staining scores distinguished HCC from hepatic metastases with 80.1% sensitivity and 77.1% specificity. These enzymes had partially overlapping intracellular distributions, ACSL4 localised to the plasma membrane and both isoforms associated with lipid droplets and the endoplasmic reticulum (ER). In conclusion, analysis of ACSL3 and ACSL4 expression can distinguish different classes of hepatic tumours.

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<![CDATA[Autophagy in the mammalian nervous system: a primer for neuroscientists]]> https://www.researchpad.co/article/N0e73c24f-a1fe-42b7-b578-a6cd3225d1d0

Abstract

Autophagy refers to the lysosomal degradation of damaged or superfluous components and is essential for metabolic plasticity and tissue integrity. This evolutionarily conserved process is particularly vital to mammalian post-mitotic cells such as neurons, which face unique logistical challenges and must sustain homoeostasis over decades. Defective autophagy has pathophysiological importance, especially for human neurodegeneration. The present-day definition of autophagy broadly encompasses two distinct yet related phenomena: non-selective and selective autophagy. In this minireview, we focus on established and emerging concepts in the field, paying particular attention to the physiological significance of macroautophagy and the burgeoning world of selective autophagy pathways in the context of the vertebrate nervous system. By highlighting established basics and recent breakthroughs, we aim to provide a useful conceptual framework for neuroscientists interested in autophagy, in addition to autophagy enthusiasts with an eye on the nervous system.

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<![CDATA[Effect of UVA1 on hypertrophic scarring in the rabbit ear model]]> https://www.researchpad.co/article/N0ef987b5-8402-4f27-bd1f-20d45877e5a4

Abstract

Hypertrophic scars (HTSs) are common and cause functional and psychological morbidity. UVA1 (340–400 nm) phototherapy has been previously shown to be effective in the treatment of localized scleroderma, systemic sclerosis, and POEMS syndrome with minimal side effects, all of which are presented as collagen fibrils hyperplasia that is common with scarring in skin histology. In the present study, we aimed to investigate the impact of UVA1 on the protein expression of TGF-β signal pathway and myofibroblasts in a rabbit model of cutaneous scarring. Full-thickness skin wounds (2 cm × 5 cm in diameter) were made in New Zealand white rabbits to establish the hypertrophic scarring model. New Zealand white rabbits were divided into two treatment groups (n=30 wounds per group with an equal number of controls): medium-dose of UVA1 phototherapy group: 60 J/cm2; high-dose of UVA1 phototherapy group: 110 J/cm2. Left ears were used for treatment and the right ones were used for control. Treatment was administered five times weekly for 6 weeks. Treated and untreated control wounds were harvested at various time points and examined by histologic examination, immunohistochemical assessment, and ultrastructural evaluation. The results showed that UVA1 phototherapy caused a significant reduction in dermal thickness by histological features, whereas the scar index was descended significantly in both medium- and high-dose UVA1 groups compared with the control group. Examination of immunohistochemistry also revealed a marked suppression of tissue growth factor-β (TGF-β) (both medium- and high-dose), α smooth muscle actin (α-SMA) (only high-dose), and tissue inhibitor of metalloproteinase 1 (TIMP-1) (only high-dose), and apparent increase in matrix metalloproteinases (MMP-1) (both medium- and high-dose) compared with the control. The ultrastructural evaluation showed the collagen fibers’ diameter had shrunk, and that fibroblastic cytoplasm was not affluent and in a quiescent stage. These findings of the present study suggested that administration of UVA1 irradiation is effective to improve the experimental HTS model and raises a possibility of the therapeutic approach of UVA1 in the scar. Although not directly examined in the present study, MMP inhibition is hypothesized to be responsible for this effect. However, early UVA1 treatment could not prevent the formation of scar model.

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