Regulation of Mammalian Mitochondrial Gene Expression: Recent Advances.
Ontology highlight
ABSTRACT:
SUBMITTER: Pearce SF
PROVIDER: S-EPMC5538620 | biostudies-other | 2017 Aug
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Synthetic regulation of gene expression provides a powerful approach to reprogram molecular and cellular processes and test the function of specific genes and gene products. In the last decade, optogenetic systems that allow light-dependent gene regulation have become valuable tools, providing tight spatiotemporal control of protein levels. Here we discuss and build on recent optogenetic approaches for regulating gene expression in mammalian cells using cryptochrome 2 (CRY2), a photoreceptor protein from Arabidopsis. We provide detailed protocols for using light to manipulate activity of a CRY2-based engineered photoactivatable Cre DNA recombinase, and to induce or disrupt transcription factor function. In addition, we provide instructions and software for building an inexpensive Rasberry-Pi-based programable LED device for optogenetic experiments, delivering pulsed light with customized control of illumination duration, frequency, and intensity.
| S-EPMC6684405 | biostudies-literature
Project description:Ever since its discovery, the double-stranded DNA contained in the mitochondria of eukaryotes has fascinated researchers because of its bacterial endosymbiotic origin, crucial role in encoding subunits of the respiratory complexes, compact nature, and specific inheritance mechanisms. In the last few years, high-throughput sequencing techniques have accelerated the sequencing of mitochondrial genomes (mitogenomes) and uncovered the great diversity of organizations, gene contents, and modes of replication and transcription found in living eukaryotes. Some early divergent lineages of unicellular eukaryotes retain certain synteny and gene content resembling those observed in the genomes of alphaproteobacteria (the inferred closest living group of mitochondria), whereas others adapted to anaerobic environments have drastically reduced or even lost the mitogenome. In the three main multicellular lineages of eukaryotes, mitogenomes have pursued diverse evolutionary trajectories in which different types of molecules (circular versus linear and single versus multipartite), gene structures (with or without self-splicing introns), gene contents, gene orders, genetic codes, and transfer RNA editing mechanisms have been selected. Whereas animals have evolved a rather compact mitochondrial genome between 11 and 50 Kb in length with a highly conserved gene content in bilaterians, plants exhibit large mitochondrial genomes of 66 Kb to 11.3 Mb with large intergenic repetitions prone to recombination, and fungal mitogenomes have intermediate sizes of 12 to 236 Kb.
| S-EPMC7194472 | biostudies-literature
Project description:Hemophilia is a monogenic mutational disease affecting coagulation factor VIII or factor IX genes. The palliative treatment of choice is based on the use of safe and effective recombinant clotting factors. Advanced therapies will be curative, ensuring stable and durable concentrations of the defective circulating factor. Results have so far been encouraging in terms of levels and times of expression using mainly adeno-associated vectors. However, these therapies are associated with immunogenicity and hepatotoxicity. Optimizing the vector serotypes and the transgene (variants) will boost clotting efficacy, thus increasing the viability of these protocols. It is essential that both physicians and patients be informed about the potential benefits and risks of the new therapies, and a register of gene therapy patients be kept with information of the efficacy and long-term adverse events associated with the treatments administered. In the context of hemophilia, gene therapy may result in (particularly indirect) cost savings and in a more equitable allocation of treatments. In the case of hemophilia A, further research is needed into how to effectively package the large factor VIII gene into the vector; and in the case of hemophilia B, the priority should be to optimize both the vector serotype, reducing its immunogenicity and hepatotoxicity, and the transgene, boosting its clotting efficacy so as to minimize the amount of vector administered and decrease the incidence of adverse events without compromising the efficacy of the protein expressed.
| S-EPMC8306493 | biostudies-literature
Project description:Mast cells are innate immune cells that intersect with the adaptive immunity and play a crucial role in the initiation of allergic reactions and the host defense against certain parasites and venoms. When activated in an allergen- and immunoglobulin E (IgE)-dependent manner, these cells secrete a large variety of allergenic mediators that are pre-stored in secretory granules or de novo–synthesized. Traditionally, studies have predominantly focused on understanding this mechanism of mast cell activation and regulation. Along this line of study, recent studies have shed light on what structural features are required for allergens and how IgE, particularly anaphylactic IgE, is produced. However, the last few years have seen a flurry of new studies on IgE-independent mast cell activation, particularly via Mrgprb2 (mouse) and MRGPRX2 (human). These studies have greatly advanced our understanding of how mast cells exert non-histaminergic itch, pain, and drug-induced pseudoallergy by interacting with sensory neurons. Recent studies have also characterized mast cell activation and regulation by interleukin-33 (IL-33) and other cytokines and by non-coding RNAs. These newly identified mechanisms for mast cell activation and regulation will further stimulate the allergy/immunology community to develop novel therapeutic strategies for treatment of allergic and non-allergic diseases.
| S-EPMC7096214 | biostudies-literature
Project description:Over the past 15 years, the emotion regulation perspective has been widely integrated into theoretical and applied contexts in clinical psychology and beyond. Recent refinements to behavioral, subjective, psychophysiological and neuroimaging methods allow emotion regulation to be captured and assessed in the laboratory with greater precision. Technological advances enabling investigators to leverage information from multiple modalities are increasingly accessible, and as such, will further efforts to generate testable hypotheses about specific mechanisms implicated in emotion regulation and difficulties therein. In combination with theory-driven design, progressively sophisticated methods for laboratory assessment have potential to further emotion regulation as both a valid scientific construct and a useful paradigm for human emotion and behavior that has applicability to both clinical and non-clinical contexts.
| S-EPMC6092030 | biostudies-literature
Project description:Since the early studies on the resolution and reconstitution of the oxidative phosphorylation system from animal mitochondria, coupling factor B was recognized as an essential component of the machinery responsible for energy-driven ATP synthesis. At the phenomenological level, factor B was agreed to lie at the interface of energy transfer between the respiratory chain and the ATP synthase complex. However, biochemical characterization of the factor B polypeptide has proved difficult. It was not until 1990 that the N-terminal amino acid sequence of bovine mitochondrial factor B was reported, which followed, a decade later, by the report describing the amino acid sequence of full-length human factor B and its functional characterization. The present review summarizes the recent advances in structure-functional studies of factor B, including its recently determined crystal structure at 0.96 A resolution. Ectopic expression of human factor B in cultured animal cells has unexpectedly revealed its role in shaping mitochondrial morphology. The supramolecular assembly of ATP synthase as dimer ribbons at highly curved apices of the mitochondrial cristae was recently suggested to optimize ATP synthesis under proton-limited conditions. We propose that the binding of the ATP synthase dimers with factor B tetramers could be a means to enhance the efficiency of the terminal step of oxidative phosphorylation in animal mitochondria.
| S-EPMC2880480 | biostudies-literature
Project description:Purpose of reviewWe aim to review the most recent findings in genomics of sarcoidosis and highlight the gaps in the field.Recent findingsOriginal explorations of sarcoidosis subphenotypes, including cases associated with the World Trade Center and ocular sarcoidosis, have identified novel risk loci. Innovative gene--environment interaction studies utilizing modern analytical techniques have discovered risk loci associated with smoking and insecticide exposure. The application of whole-exome sequencing has identified genetic variants associated with persistent sarcoidosis and rare functional variations. A single epigenomics study has provided background knowledge of DNA methylation mechanisms in comparison with gene expression data. The application of machine-learning techniques has suggested new drug repositioning for the treatment of sarcoidosis. Several gene expression studies have identified prominent inflammatory pathways enriched in the affected tissue.SummaryCertainly, sarcoidosis research has recently advanced in the exploration of disease subphenotypes, utilizing novel analytical techniques, and including measures of clinical variation. Nevertheless, large-scale and diverse cohorts investigated with advanced sequencing methods, such as whole-genome and single-cell RNA sequencing, epigenomics, and meta-analysis coupled with cutting-edge analytic approaches, when employed, will broaden and translate genomics findings into clinical applications, and ultimately open venues for personalized medicine.
| S-EPMC7735660 | biostudies-literature
Project description:Recent attention has been given to the role of emotion regulation in the development and maintenance of psychopathology, and the psychosocial literature on emotion regulation has been growing rapidly over the past decade. However, knowledge about the genetic etiology of emotion regulation facets has been slower to develop. The present paper aims to briefly introduce the various constructs that fall under the umbrella of emotion regulation; provide an overview of behavioral genetic methods; summarize the empirical studies of emotion regulation twin studies; introduce molecular genetic methods; review the recent molecular genetic studies on emotion regulation; and provide future directions for research.
| S-EPMC5004926 | biostudies-literature
Project description:There has been significant progress in the field of gene therapy toward clinical application in recent years. Cardiac gene therapy has followed this trend, but at a slower pace compared to therapies targeting retinal, spinal, and blood disorders. New approaches targeting monogenic disorders are being developed at a rapid pace and studies in large animal models show promise. Meanwhile, several clinical trials are underway to prove the efficacy of gene therapy for cardiovascular diseases such as heart failure. In this concise review, we attempt to summarize recent highlights in technological advancements, preclinical studies, and clinical trials of cardiac gene therapy.
| S-EPMC7544018 | biostudies-literature
Project description:There is great interest in developing gene therapies for many disease indications, including cancer. However, successful delivery of nucleic acids to tumor cells is a major challenge, and in vivo efficacy is difficult to predict. Cancer theranostics is an approach combining anti-tumor therapy with imaging or diagnostic capabilities, with the goal of monitoring successful delivery and efficacy of a therapeutic agent in a tumor. Successful theranostics must maintain a high degree of anticancer targeting and efficacy while incorporating high-contrast imaging agents that are nontoxic and compatible with clinical imaging modalities. This review highlights recent advancements in theranostic strategies, including imaging technologies and genetic engineering approaches. Graphical Abstract.
| S-EPMC8562678 | biostudies-literature