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Ximena Calle, Valeria Garrido-Moreno, Erik Lopez-Gallardo, Ignacio Norambuena-Soto, Daniela Martínez, Allan Peñaloza-Otárola, Angelo Troncossi, Alejandra Guerrero-Moncayo, Angélica Ortega, Vinicius Maracaja-Coutinho, Valentina Parra, Mario Chiong, Sergio Lavandero
First published: 30 May 2022
Mitochondrial E3 ubiquitin ligase 1 (MUL1) is a mitochondrial outer membrane-anchored protein-containing transmembrane domain in its N- and C-terminal regions, where both are exposed to the cytosol. Interestingly the C-terminal region has a RING finger domain responsible for its E3 ligase activity, as ubiquitin or in SUMOylation, interacting with proteins related to mitochondrial fusion and fission, cell survival, and tumor suppressor process, such as Akt. Therefore, MUL1 is involved in various cellular processes, such as mitochondrial dynamics, inter-organelle communication, proliferation, mitophagy, immune response, inflammation and cell apoptosis. MUL1 is expressed at a higher basal level in the heart, immune system organs, and blood. Here, we discuss the role of MUL1 in mitochondrial dynamics and its function in various pathological models, both in vitro and in vivo. In this context, we describe the role of MUL1 in: (1) the inflammatory response, by regulating NF-κB activity; (2) cancer, by promoting cell death and regulating exonuclear function of proteins, such as p53; (3) neurological diseases, by maintaining communication with other organelles and interacting with proteins to eliminate damaged organelles and; (4) cardiovascular diseases, by maintaining mitochondrial fusion/fission homeostasis. In this review, we summarize the latest advances in the physiological and pathological functions of MUL1. We also describe the different substrates of MUL1, acting as a positive or negative regulator in various pathologies associated with mitochondrial dysfunction. In conclusion, MUL1 could be a potential key target for the development of therapies that focus on ensuring the functionality of the mitochondrial network and, furthermore, the quality control of intracellular components by synchronously modulating the activity of different cellular mechanisms involved in the aforementioned pathologies. This, in turn, will guide the development of targeted therapies.
Gian Marco Vita, Giovanna De Simone, Elisabetta De Marinis, Clara Nervi, Paolo Ascenzi, Alessandra di Masi
First published: 17 May 2022
Serum albumin (SA) is the most abundant protein in plasma and represents the main carrier of endogenous and exogenous compounds. Several evidence supports the notion that SA binds single and double-stranded deoxynucleotides and ribonucleotides at two sites, with values of the dissociation equilibrium constant (i.e., Kd) ranging from micromolar to nanomolar values. This can be relevant from a physiological and pathological point of view, as in human plasma circulates cell-free nucleic acids (cfNAs), released by different tissues via apoptosis, necrosis, and secretions, circulates as single and double-stranded NAs. Albeit SA shows low hydrolytic reactivity toward DNA and RNA, the high plasma concentration of this protein and the occurrence of several SA receptors may be pivotal for sequestering and hydrolyzing cfNAs. Therefore, pathological conditions like cancer, characterized by altered levels of human SA or by altered SA post-translational modifications, may influence cfNAs distribution and metabolism. Besides, the stability, solubility, biocompatibility, and low immunogenicity make SA a golden share for biotechnological applications related to the delivery of therapeutic NAs (TNAs). Indeed, pre-clinical studies report the therapeutic potential of SA:TNAs complexes in precision cancer therapy. Here, the molecular and biotechnological implications of SA:NAs interaction are discussed, highlighting new perspectives on SA plasmatic functions.
SPECIAL ISSUE CALL FOR PAPERS
GUEST EDITOR: Mandeep Kaur, University of the Witwatersrand
Deadline extension for manuscript submission 30 September 2022
Expected issue publication will be summer 2023
NEW VIRTUAL ISSUES
Tingting Han, Hailin Cong, Bing Yu, Youqing Shen
First published: 11 July 2022
Biomedicine is developing rapidly in the 21st century. Among them, the qualitative and quantitative analysis of peptide biomarkers is of considerable importance for the diagnosis and therapy of diseases and the quality evaluation of drugs and food. The identification and quantitative analysis of peptides have been going on for decades. Traditionally, immunoassays or biological assays are generally used to quantify peptides in biological matrices. However, the selectivity and sensitivity of these methods cannot meet the requirements of the application. The separation and analysis technique of liquid chromatography-mass spectrometry (LC–MS) supplies a reliable alternative. In contrast to immunoassays, LC–MS methods are capable of providing the analytical prowess necessary to satisfy the demands of peptide biomarker research in the life sciences arena. This review article provides a historical account of the in-roads made by LC–MS technology for the detection of peptide biomarkers in the past 10 years, with the focus on the qualification/quantification developments and their applications.
Sina Mahdiani, Navid Omidkhoda, Shadi Heidari, A. Wallace Hayes, Gholamreza Karimi
First published: 21 July 2022
Humans are continuously exposed to environmental, occupational, consumer and household products, food, and pharmaceutical substances. Luteolin, a flavone from the flavonoids family of compounds, is found in different fruits and vegetables. LUT is a strong anti-inflammatory (via inhibition of NF-κB, ERK1/2, MAPK, JNK, IL-6, IL-8, and TNF-α) and antioxidant agent (reducing ROS and enhancement of endogenous antioxidants). LUT can chelate transition metal ions responsible for ROS generation and consequently repress lipoxygenase. It has been proven that NF-κB, as a commom cellular pathway plays a considerable role in the progression of inflammatory process and stimulates the expression of genes encoding inducible pro-inflammatory enzymes (iNOS and COX-2) and cytokines including IL-1β, IL-6, and TNF-α. This review summarizes the available literature discussing LUT and its potential protective role against pharmaceuticals-, metals-, and environmental compounds-induced toxicities. Furthermore, the review explains the involved protective mechanisms, especially inhibition of the NF-κB pathway.
Biotechnology and Applied Biochemistry
SM Evangelene Christy, V Arun
First published: 05 August 2022
A promoter is a region in the genome sequence located upstream of the transcription start site comprising cis acting elements that initiates and regulates the transcription of an associated genes and restriction endonucleases. As the need for genetically engineered plants has widened, the requirement to develop methods to optimize the control of transgene expression has also increased. Therefore, analyzing the functionality of the promoter is very important in understanding the target gene expression. The widespread use of viral constitutive promoters (cauliflower mosaic virus, CaMV35) has raised concerns about the safety and containment of transgene in the environment. Hence isolation and characterization of novel promoters using fast and efficient genetic engineering tools is the need of the hour. The present study, for the first time, describes the isolation and characterization of a novel constitutive promoter driving ubiquitin E3 ligase from the plant Coleus amboinicus, a perennial herb, of the Lamiaceae family. The functionality of the isolated promoter was demonstrated using the β -glucuronidase as a reporter in tobacco var Petit havana. The development of blue color in the tobacco leaves indicated the presence of a functional promoter.
Zhihua Jin, Tong Lu, Wenjun Feng, Qingchao Jin, Zhige Wu, Yu Yang
First published: 20 July 2022
By screening the strains and testing different combinations of diverse bacteria, we developed a compound bacterial agent composed of 5 g Bacillus amyloliquefaciens (B2), 10 g Pseudomonas aeruginosa (F4), 5 g Paenibacillus lautus (303), and 10 ml composite strains (DOD) for the degradation of household food waste (HFW). The final mass loss of HFW in aerobic composting with the compound bacteria agent B2+F4+303+DOD (group C) was 84.52%, increased by 20.83% over that loss in natural composting (group A). Analysis of 16S rRNA high-throughput sequencing showed that the phyla in group A and group C mainly included Firmicutes, Proteobacteria, and Cyanobacteria. At the genus level, Pediococcus was the dominant genus in group A, of which the microbial community performed better in maintaining a stable microbial system in the later stage of composting, while Weissella accounted for a larger proportion of group C, which acted well in reducing the final mass of composting. Ochrobactrum was closely related to the removal of odors in the early stage of group C. The relative abundance of compound bacterial agents was always at a rather low level, suggesting that it affected the composting process by changing the proportion of dominant bacteria in the compost.
Biochemistry and Molecular Biology Education
Toryn M. Poolman, Andrea Townsend-Nicholson, Amanda Cain
First published: 16 August 2022
The final year of a biochemistry degree is usually a time to experience research. However, laboratory-based research projects were not possible during COVID-19. Instead, we used open datasets to provide computational research projects in metagenomics to biochemistry undergraduates (80 students with limited computing experience). We aimed to give the students a chance to explore any dataset, rather than use a small number of artificial datasets (~60 published datasets were used). To achieve this, we utilized Google Colaboratory (Colab), a virtual computing environment. Colab was used as a framework to retrieve raw sequencing data (analyzed with QIIME2) and generate visualizations. Setting up the environment requires no prior experience; all students have the same drive structure and notebooks can be shared (for synchronous sessions). We also used the platform to combine multiple datasets, perform a meta-analysis, and allowed the students to analyze large datasets with 1000s of subjects and factors. Projects that required increased computational resources were integrated with Google Cloud Compute. In future, all research projects can include some aspects of reanalyzing public data, providing students with data science experience. Colab is also an excellent environment in which to develop data skills in multiple languages (e.g., Perl, Python, Julia).
Martín L. Mayta, Marcela Dotto, Elena G. Orellano, Adriana R. Krapp
First published: 27 July 2022
The CRISPR/Cas9 system is widely used for editing genes in various organisms and is a very useful tool due to its versatility, simplicity, and efficiency. To teach its principles to post-graduate students we designed a laboratory activity to obtain and analyze PDS3 mutants in Arabidopsis thaliana plants consisting of: 1) Design of guide RNAs using bioinformatics tools; 2) plant transformation (which is optional depending on the length of the course); 3) observation and evaluation of the mutant’s phenotypes in the Phytoene desaturase (PDS3) gene, which exhibit an albino phenotype and different degrees of mosaicism in the editing events we evaluated; 4) PCR amplification of a fragment that includes the mutated region followed by analysis of single-stranded DNA conformation polymorphisms (SSCP) using native polyacrylamide gel electrophoresis and silver nitrate staining to detect changes in the amplicon sequence due to gene editing. Through SSCP, the students were able to distinguish between homozygous and heterozygous edited plants. A highlight feature of this protocol is the visualization and detection of the mutation/edition without sequencing the edited fragment.
Did you know? Wiley and Jisc just signed an agreement that allows UK authors to publish Open Access in the IUBMB Journals at no cost to them.
Thanks to a partnership our publisher Wiley has signed with Jisc, certain UK institutions now have full access to journals published by Wiley, including the IUBMB Journals. Further, the partnership enables authors at participating UK institutions to publish open access at no cost to them in the IUBMB Journals. Payment of the associated Article Publication Charges (APC) would be covered via the partnership, and authors will not need to cover the APCs from their own pockets.
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Molecular Aspects of Medicine
Volume 86 (August 2022) 101066
by Juliane Hermann, Leon Schurgers, Vera Jankowski
Aspects of Molecular Medicine
Make Aspects of Molecular Medicine – the new complementary open access sister journal of Molecular Aspects of Medicine – the home for your next research paper. Find out more!