scholarly journals Glycosome heterogeneity in kinetoplastids

2021 ◽  
Author(s):  
Logan P. Crowe ◽  
Meredith T. Morris
Keyword(s):  
Flow Cytometry ◽  
Protein Import ◽  
Therapeutic Targets ◽  
Protein Composition ◽  
Recent Advances ◽  
Cellular Machinery ◽  
And Function ◽  
Organelle Sorting

Kinetoplastid parasites have essential organelles called glycosomes that are analogous to peroxisomes present in other eukaryotes. While many of the processes that regulate glycosomes are conserved, there are several unique aspects of their biology that are divergent from other systems and may be leveraged as therapeutic targets for the treatment of kinetoplastid diseases. Glycosomes are heterogeneous organelles that likely exist as sub-populations with different protein composition and function in a given cell, between individual cells, and between species. However, the limitations posed by the small size of these organelles makes the study of this heterogeneity difficult. Recent advances in the analysis of small vesicles by flow-cytometry provide an opportunity to overcome these limitations. In this review, we describe studies that document the diverse nature of glycosomes and propose an approach to using flow cytometry and organelle sorting to study the diverse composition and function of these organelles. Because the cellular machinery that regulates glycosome protein import and biogenesis is likely to contribute, at least in part, to glycosome heterogeneity we highlight some ways in which the glycosome protein import machinery differs from that of peroxisomes in other eukaryotes.

scholarly journals Post-transcriptional control of mitochondrial protein composition in changing environmental conditions

2020 ◽  
Vol 48 (6) ◽  
pp. 2565-2578
Author(s):  
Tatsuhisa Tsuboi ◽  
Jordan Leff ◽  
Brian M. Zid
Keyword(s):  
Environmental Conditions ◽  
Transcriptional Control ◽  
Protein Import ◽  
Mitochondrial Protein ◽  
Protein Composition ◽  
Mrna Translation ◽  
Mitochondrial Structure ◽  
Age Related ◽  
And Function ◽  
Post Transcriptional Regulation

In fluctuating environmental conditions, organisms must modulate their bioenergetic production in order to maintain cellular homeostasis for optimal fitness. Mitochondria are hubs for metabolite and energy generation. Mitochondria are also highly dynamic in their function: modulating their composition, size, density, and the network-like architecture in relation to the metabolic demands of the cell. Here, we review the recent research on the post-transcriptional regulation of mitochondrial composition focusing on mRNA localization, mRNA translation, protein import, and the role that dynamic mitochondrial structure may have on these gene expression processes. As mitochondrial structure and function has been shown to be very important for age-related processes, including cancer, metabolic disorders, and neurodegeneration, understanding how mitochondrial composition can be affected in fluctuating conditions can lead to new therapeutic directions to pursue.

scholarly journals TOM20-mediated transfer of Bcl2 from ER to MAM and mitochondria upon induction of apoptosis

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Lisenn Lalier ◽  
Vincent Mignard ◽  
Marie-Pierre Joalland ◽  
Didier Lanoé ◽  
Pierre-François Cartron ◽  
...  
Keyword(s):  
Protein Import ◽  
Glioma Cells ◽  
Mitochondrial Outer Membrane ◽  
Mitochondrial Localization ◽  
Antiapoptotic Protein ◽  
Mitochondrial Transfer ◽  
Small Domain ◽  
Induction Of Apoptosis ◽  
And Function

AbstractIn this work, we have explored the subcellular localization of Bcl2, a major antiapoptotic protein. In U251 glioma cells, we found that Bcl2 is localized mainly in the ER and is translocated to MAM and mitochondria upon induction of apoptosis; this mitochondrial transfer was not restricted to the demonstrator cell line, even if cell-specific modulations exist. We found that the Bcl2/mitochondria interaction is controlled by TOM20, a protein that belongs to the protein import machinery of the mitochondrial outer membrane. The expression of a small domain of interaction of TOM20 with Bcl2 potentiates its anti-apoptotic properties, which suggests that the Bcl2–TOM20 interaction is proapoptotic. The role of MAM and TOM20 in Bcl2 apoptotic mitochondrial localization and function has been confirmed in a yeast model in which the ER–mitochondria encounter structure (ERMES) complex (required for MAM stability in yeast) has been disrupted. Bcl2–TOM20 interaction is thus an additional player in the control of apoptosis.

scholarly journals Impact of DNA methylation on 3D genome structure

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Diana Buitrago ◽  
Mireia Labrador ◽  
Juan Pablo Arcon ◽  
Rafael Lema ◽  
Oscar Flores ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Chromatin Structure ◽  
Chromatin Condensation ◽  
Genome Structure ◽  
Dna Methyltransferases ◽  
Model System ◽  
Structure And Function ◽  
3D Genome ◽  
Cellular Machinery ◽  
And Function

AbstractDetermining the effect of DNA methylation on chromatin structure and function in higher organisms is challenging due to the extreme complexity of epigenetic regulation. We studied a simpler model system, budding yeast, that lacks DNA methylation machinery making it a perfect model system to study the intrinsic role of DNA methylation in chromatin structure and function. We expressed the murine DNA methyltransferases in Saccharomyces cerevisiae and analyzed the correlation between DNA methylation, nucleosome positioning, gene expression and 3D genome organization. Despite lacking the machinery for positioning and reading methylation marks, induced DNA methylation follows a conserved pattern with low methylation levels at the 5’ end of the gene increasing gradually toward the 3’ end, with concentration of methylated DNA in linkers and nucleosome free regions, and with actively expressed genes showing low and high levels of methylation at transcription start and terminating sites respectively, mimicking the patterns seen in mammals. We also see that DNA methylation increases chromatin condensation in peri-centromeric regions, decreases overall DNA flexibility, and favors the heterochromatin state. Taken together, these results demonstrate that methylation intrinsically modulates chromatin structure and function even in the absence of cellular machinery evolved to recognize and process the methylation signal.

scholarly journals Recent advances in understanding and managing psoriatic arthritis

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2670 ◽  
Author(s):  
Dafna D. Gladman
Keyword(s):  
Psoriatic Arthritis ◽  
Early Diagnosis ◽  
Clinical Laboratory ◽  
Joint Damage ◽  
Screening Tools ◽  
Therapeutic Interventions ◽  
Joint Disease ◽  
New Therapeutic Approaches ◽  
Recent Advances ◽  
And Function

This article reviews recent advances in psoriatic arthritis (PsA) over the past several years with emphasis on early diagnosis, better understanding of pathogenesis, and new therapeutic approaches. Early diagnosis is important, since people who present late do not fare as well. There are a number of clinical, laboratory, and ultrasound features that can help identify patients destined to develop PsA, and several screening tools have been developed. It is recognized that genetic and epigenetic factors, as well as T cells and cytokines, play a role in the pathogenesis of PsA, and several targets have been identified for therapeutic interventions. New therapies have been developed and tested in PsA and have been found to be highly effective for both skin and joint manifestations of the disease. The expectation is that, in the future, PsA patients will be treated early and more aggressively and that there will not be significant progression of joint damage. Moreover, with effective treatment of the skin and joint disease and management of risk factors for the comorbidities, we can expect to reduce their occurrence and further reduce the excess mortality and reduced quality of life and function in these patients.

scholarly journals Intraendosomal flow cytometry: A novel approach to analyze the protein composition of antigen-loaded endosomes

2012 ◽  
Vol 42 (8) ◽  
pp. 2187-2190 ◽  
Author(s):  
Matthias Zehner ◽  
Judith Rauen ◽  
Achmet I. Chasan ◽  
Maria Embgenbroich ◽  
Marcel G. Camps ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Protein Composition ◽  
Novel Approach

Dimerization of TOC receptor GTPases and its implementation for the control of protein import into chloroplasts

2011 ◽  
Vol 436 (2) ◽  
pp. e1-e2 ◽  
Author(s):  
Henrik Aronsson ◽  
Paul Jarvis
Keyword(s):  
Protein Import ◽  
Control Point ◽  
Nucleotide Exchange ◽  
Biochemical Journal ◽  
Exact Function ◽  
Translocation Mechanism ◽  
Loaded State ◽  
Outer Envelope Membrane ◽  
And Function

Pre-protein import into chloroplasts is facilitated by multiprotein translocon complexes in the envelope membranes. Major components of the TOC (translocon at the outer envelope membrane of chloroplasts) complex are the receptor proteins Toc33 and Toc159. These two receptors are related GTPases, and they are predicted to engage in homodimerization and/or heterodimerization. Although such dimerization has been studied extensively, its exact function in vivo remains elusive. In this issue of the Biochemical Journal, Oreb et al. present evidence that homodimerization of Toc33 prevents nucleotide exchange, thereby locking the receptor in the GDP-loaded state and preventing further activity. Pre-protein arrival is proposed to release this lock, through disruption of the dimer and subsequent nucleotide exchange. The Toc33-bound pre-protein is then able to progress to downstream steps in the translocation mechanism, with GTP hydrolysis defining another important control point as well as preparing the receptor for the next pre-protein client. These new results are discussed in the context of previous findings pertaining to TOC receptor dimerization and function.

scholarly journals Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity

mSystems ◽  
2018 ◽  
Vol 3 (6) ◽  
Author(s):  
Jingwei Cai ◽  
Robert G. Nichols ◽  
Imhoi Koo ◽  
Zachary A. Kalikow ◽  
Limin Zhang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Amino Acids ◽  
Flow Cytometry ◽  
Free Radical ◽  
Gut Microbiota ◽  
Structure And Function ◽  
Metabolic Phenotyping ◽  
And Function

ABSTRACTThe gut microbiota is susceptible to modulation by environmental stimuli and therefore can serve as a biological sensor. Recent evidence suggests that xenobiotics can disrupt the interaction between the microbiota and host. Here, we describe an approach that combinesin vitromicrobial incubation (isolated cecal contents from mice), flow cytometry, and mass spectrometry- and1H nuclear magnetic resonance (NMR)-based metabolomics to evaluate xenobiotic-induced microbial toxicity. Tempol, a stabilized free radical scavenger known to remodel the microbial community structure and functionin vivo, was studied to assess its direct effect on the gut microbiota. The microbiota was isolated from mouse cecum and was exposed to tempol for 4 h under strict anaerobic conditions. The flow cytometry data suggested that short-term tempol exposure to the microbiota is associated with disrupted membrane physiology as well as compromised metabolic activity. Mass spectrometry and NMR metabolomics revealed that tempol exposure significantly disrupted microbial metabolic activity, specifically indicated by changes in short-chain fatty acids, branched-chain amino acids, amino acids, nucleotides, glucose, and oligosaccharides. In addition, a mouse study with tempol (5 days gavage) showed similar microbial physiologic and metabolic changes, indicating that thein vitroapproach reflectedin vivoconditions. Our results, through evaluation of microbial viability, physiology, and metabolism and a comparison ofin vitroandin vivoexposures with tempol, suggest that physiologic and metabolic phenotyping can provide unique insight into gut microbiota toxicity.IMPORTANCEThe gut microbiota is modulated physiologically, compositionally, and metabolically by xenobiotics, potentially causing metabolic consequences to the host. We recently reported that tempol, a stabilized free radical nitroxide, can exert beneficial effects on the host through modulation of the microbiome community structure and function. Here, we investigated a multiplatform phenotyping approach that combines high-throughput global metabolomics with flow cytometry to evaluate the direct effect of tempol on the microbiota. This approach may be useful in deciphering how other xenobiotics directly influence the microbiota.

scholarly journals The Expression and Function of Circadian Rhythm Genes in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yanan Jiang ◽  
Xiuyun Shen ◽  
Moyondafoluwa Blessing Fasae ◽  
Fengnan Zhi ◽  
Lu Chai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Pathogenic Mechanism ◽  
Research Progress ◽  
Biological Processes ◽  
And Function ◽  
Novel Therapeutic

Hepatocellular carcinoma (HCC) is among the most common and lethal form of cancer worldwide. However, its diagnosis and treatment are still dissatisfactory, due to limitations in the understanding of its pathogenic mechanism. Therefore, it is important to elucidate the molecular mechanisms and identify novel therapeutic targets for HCC. Circadian rhythm-related genes control a variety of biological processes. These genes play pivotal roles in the initiation and progression of HCC and are potential diagnostic markers and therapeutic targets. This review gives an update on the research progress of circadian rhythms, their effects on the initiation, progression, and prognosis of HCC, in a bid to provide new insights for the research and treatment of HCC.

scholarly journals Recent advances in alveolar biology: Evolution and function of alveolar proteins

2010 ◽  
Vol 173 ◽  
pp. S43-S54 ◽  
Author(s):  
Sandra Orgeig ◽  
Pieter S. Hiemstra ◽  
Edwin J.A. Veldhuizen ◽  
Cristina Casals ◽  
Howard W. Clark ◽  
...  
Keyword(s):  
Recent Advances ◽  
And Function

Bone Grafts: An Overview of Bone Remodeling, Types and Recent Advances

2021 ◽  
pp. 6101-6105
Author(s):  
Gopala Krishna Ganta ◽  
Rama Krishna Alla ◽  
Kamala Cheruvu ◽  
Bharathi Ram Guduri
Keyword(s):  
Bone Graft ◽  
Bone Remodeling ◽  
Gold Standard ◽  
Bone Grafts ◽  
Form And Function ◽  
Recent Advances ◽  
And Function ◽  
Insight Into

Bone grafts are often used to retrieve the lost bone in the most acceptable, technical and skilful manner that enables to restore the form and function of the bone. Numerous bone graft materials have been developed to fill and/or remodel the bony defects. Though, autografts were considered to be the gold standard among the grafts available; they have got some inherent disadvantages. The current research is more focused on allografts, which addressed the problems associated with autografts. This article provides an insight into the remodeling process, and various types of bone grafts currently available. Also, the emphasis was given on the recent advances of the bone grafts.

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