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Biochemical Society Transactions Feb 2021Kinetoplastid parasites have essential organelles called glycosomes that are analogous to peroxisomes present in other eukaryotes. While many of the processes that... (Review)
Review
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.
Topics: Animals; Kinetoplastida; Microbodies; Peroxisomes; Protein Transport; Protozoan Proteins
PubMed: 33439256
DOI: 10.1042/BST20190517 -
The Journal of Biological Chemistry Feb 1997
Review
Topics: 3T3 Cells; Adipocytes; Animals; CCAAT-Enhancer-Binding Proteins; Cell Differentiation; DNA-Binding Proteins; Mice; Microbodies; Models, Biological; Nuclear Proteins; Receptors, Cytoplasmic and Nuclear; Signal Transduction; Transcription Factors; Tretinoin
PubMed: 9102400
DOI: 10.1074/jbc.272.9.5367 -
The Biochemical Journal May 2023Mitochondrial β-oxidation is the most prominent pathway for fatty acid oxidation but alternative oxidative metabolism exists. Fatty acid ω-oxidation is one of these... (Review)
Review
Mitochondrial β-oxidation is the most prominent pathway for fatty acid oxidation but alternative oxidative metabolism exists. Fatty acid ω-oxidation is one of these pathways and forms dicarboxylic acids as products. These dicarboxylic acids are metabolized through peroxisomal β-oxidation representing an alternative pathway, which could potentially limit the toxic effects of fatty acid accumulation. Although dicarboxylic acid metabolism is highly active in liver and kidney, its role in physiology has not been explored in depth. In this review, we summarize the biochemical mechanism of the formation and degradation of dicarboxylic acids through ω- and β-oxidation, respectively. We will discuss the role of dicarboxylic acids in different (patho)physiological states with a particular focus on the role of the intermediates and products generated through peroxisomal β-oxidation. This review is expected to increase the understanding of dicarboxylic acid metabolism and spark future research.
Topics: Microbodies; Fatty Acids; Oxidation-Reduction; Mitochondria; Liver; Dicarboxylic Acids
PubMed: 37140888
DOI: 10.1042/BCJ20230041 -
PLoS Neglected Tropical Diseases Apr 2017Trypanosomatid parasites, including Trypanosoma and Leishmania, are the causative agents of lethal diseases threatening millions of people around the world. These... (Review)
Review
Trypanosomatid parasites, including Trypanosoma and Leishmania, are the causative agents of lethal diseases threatening millions of people around the world. These organisms compartmentalize glycolysis in essential, specialized peroxisomes called glycosomes. Peroxisome proliferation can occur through growth and division of existing organelles and de novo biogenesis from the endoplasmic reticulum. The level that each pathway contributes is debated. Current evidence supports the concerted contribution of both mechanisms in an equilibrium that can vary depending on environmental conditions and metabolic requirements of the cell. Homologs of a number of peroxins, the proteins involved in peroxisome biogenesis and matrix protein import, have been identified in T. brucei. Based on these findings, it is widely accepted that glycosomes proliferate through growth and division of existing organelles; however, to our knowledge, a de novo mechanism of biogenesis has not been directly demonstrated. Here, we review recent findings that provide support for the existence of an endoplasmic reticulum (ER)-derived de novo pathway of glycosome biogenesis in T. brucei. Two studies recently identified PEX13.1, a peroxin involved in matrix protein import, in the ER of procyclic form T. brucei. In other eukaryotes, peroxins including PEX13 have been found in the ER of cells undergoing de novo biogenesis of peroxisomes. In addition, PEX16 and PEX19 have been characterized in T. brucei, both of which are important for de novo biogenesis in other eukaryotes. Because glycosomes are rapidly remodeled via autophagy during life cycle differentiation, de novo biogenesis could provide a method of restoring glycosome populations following turnover. Together, the findings we summarize provide support for the hypothesis that glycosome proliferation occurs through growth and division of pre-existing organelles and de novo biogenesis of new organelles from the ER and that the level each mechanism contributes is influenced by glucose availability.
Topics: Autophagy; Cell Differentiation; Endoplasmic Reticulum; Leishmania; Life Cycle Stages; Membrane Proteins; Microbodies; Peroxisomes; Protozoan Proteins; Trypanosoma brucei brucei
PubMed: 28426655
DOI: 10.1371/journal.pntd.0005333 -
Biochimica Et Biophysica Acta Dec 2006Yeast and filamentous fungi are important model organisms in microbody research. The value of these organisms as models for higher eukaryotes is underscored by the... (Review)
Review
Yeast and filamentous fungi are important model organisms in microbody research. The value of these organisms as models for higher eukaryotes is underscored by the observation that the principles of various aspects of microbody biology are strongly conserved from lower to higher eukaryotes. This has allowed to resolve various peroxisome-related functions, including peroxisome biogenesis disorders in man. This paper summarizes the major advances in microbody research using fungal systems and specifies specific properties and advantages/disadvantages of the major model organisms currently in use.
Topics: Mitosporic Fungi; Models, Biological; Peroxisomes; Yeasts
PubMed: 17050005
DOI: 10.1016/j.bbamcr.2006.09.014 -
Advances in Experimental Medicine and... 2013Whereas P-bodies are intimately linked to the cytoplasmic RNA decay machinery, stress granules harbor stalled translation initiation complexes that accumulate upon... (Review)
Review
Whereas P-bodies are intimately linked to the cytoplasmic RNA decay machinery, stress granules harbor stalled translation initiation complexes that accumulate upon stress-induced translation arrest. In this Chapter, we reflect on the relationship between P-bodies and stress granules. In mammalian cells, the two structures can be clearly distinguished from each other using specific protein or RNA markers, but they also share many proteins and mRNAs. While the formation of P-bodies and stress granules is coordinately triggered by stress, their assembly appears to be regulated independently by different pathways. Under certain types of stress, P-bodies frequently dock with stress granules, and overexpressing certain proteins that localize to both structures can cause P-body/stress granule fusion. Currently available data suggest that these self-assembling compartments are controlled by flux of mRNAs within the cytoplasm, and that their assembly mirrors the translation and degradation rates of their component mRNAs.
Topics: Animals; Biological Transport; Cytoplasmic Granules; Fluorescent Antibody Technique; Gene Expression Regulation; Humans; MicroRNAs; Microbodies; Protein Biosynthesis; RNA Stability; RNA, Messenger; Ribonucleoproteins; Saccharomyces cerevisiae; Stress, Physiological
PubMed: 23224972
DOI: 10.1007/978-1-4614-5107-5_12 -
Proceedings. Biological Sciences Aug 2015Colour, derived primarily from melanin and/or carotenoid pigments, is integral to many aspects of behaviour in living vertebrates, including social signalling, sexual... (Review)
Review
Colour, derived primarily from melanin and/or carotenoid pigments, is integral to many aspects of behaviour in living vertebrates, including social signalling, sexual display and crypsis. Thus, identifying biochromes in extinct animals can shed light on the acquisition and evolution of these biological traits. Both eumelanin and melanin-containing cellular organelles (melanosomes) are preserved in fossils, but recognizing traces of ancient melanin-based coloration is fraught with interpretative ambiguity, especially when observations are based on morphological evidence alone. Assigning microbodies (or, more often reported, their 'mouldic impressions') as melanosome traces without adequately excluding a bacterial origin is also problematic because microbes are pervasive and intimately involved in organismal degradation. Additionally, some forms synthesize melanin. In this review, we survey both vertebrate and microbial melanization, and explore the conflicts influencing assessment of microbodies preserved in association with ancient animal soft tissues. We discuss the types of data used to interpret fossil melanosomes and evaluate whether these are sufficient for definitive diagnosis. Finally, we outline an integrated morphological and geochemical approach for detecting endogenous pigment remains and associated microstructures in multimillion-year-old fossils.
Topics: Animals; Biological Evolution; Fossils; Melanins; Melanosomes; Microbodies; Pigmentation; Vertebrates
PubMed: 26290071
DOI: 10.1098/rspb.2015.0614 -
FEBS Letters Apr 1999There is a vast body of literature on the quality control of protein folding and assembly into multisubunit complexes. Such control takes place everywhere in the cell.... (Review)
Review
There is a vast body of literature on the quality control of protein folding and assembly into multisubunit complexes. Such control takes place everywhere in the cell. The correcting mechanisms involve cytosolic and organellar proteases; the result of such control is individual molecules with proper structure and individual complexes both with proper stoichiometry and proper structure. Obviously, the formation of organelles as such requires some additional criteria of correctness and some new mechanisms of their implementation. It is proposed in this article that the ability to carry out an integral (key) function may serve as a criterion of correct organelle assembly and that autophagy can be accepted as a mechanism eliminating the assembly mistakes.
Topics: Chloroplasts; Endoplasmic Reticulum; Microbodies; Mitochondria; Organelles; Protein Folding; Protein Processing, Post-Translational
PubMed: 10218476
DOI: 10.1016/s0014-5793(99)00344-0 -
Cell Reports Dec 2020Soluble forms of angiotensin-converting enzyme 2 (ACE2) have recently been shown to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We...
Soluble forms of angiotensin-converting enzyme 2 (ACE2) have recently been shown to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We report on an improved soluble ACE2, termed a "microbody," in which the ACE2 ectodomain is fused to Fc domain 3 of the immunoglobulin (Ig) heavy chain. The protein is smaller than previously described ACE2-Ig Fc fusion proteins and contains an H345A mutation in the ACE2 catalytic active site that inactivates the enzyme without reducing its affinity for the SARS-CoV-2 spike. The disulfide-bonded ACE2 microbody protein inhibits entry of SARS-CoV-2 spike protein pseudotyped virus and replication of live SARS-CoV-2 in vitro and in a mouse model. Its potency is 10-fold higher than soluble ACE2, and it can act after virus bound to the cell. The microbody inhibits the entry of β coronaviruses and virus with the variant D614G spike. The ACE2 microbody may be a valuable therapeutic for coronavirus disease 2019 (COVID-19) that is active against viral variants and future coronaviruses.
Topics: Amino Acid Sequence; Angiotensin-Converting Enzyme 2; Animals; Antiviral Agents; COVID-19; Disease Models, Animal; Disulfides; Female; HEK293 Cells; Humans; Immunoglobulin Fc Fragments; Male; Mice, Transgenic; Microbodies; Protein Domains; Protein Multimerization; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Virion; Virus Internalization
PubMed: 33326798
DOI: 10.1016/j.celrep.2020.108528 -
Biochimica Et Biophysica Acta May 2016Peroxisomes of organisms belonging to the protist group Kinetoplastea, which include trypanosomatid parasites of the genera Trypanosoma and Leishmania, are unique in... (Review)
Review
Peroxisomes of organisms belonging to the protist group Kinetoplastea, which include trypanosomatid parasites of the genera Trypanosoma and Leishmania, are unique in playing a crucial role in glycolysis and other parts of intermediary metabolism. They sequester the majority of the glycolytic enzymes and hence are called glycosomes. Their glycosomal enzyme content can vary strongly, particularly quantitatively, between different trypanosomatid species, and within each species during its life cycle. Turnover of glycosomes by autophagy of redundant ones and biogenesis of a new population of organelles play a pivotal role in the efficient adaptation of the glycosomal metabolic repertoire to the sudden, major nutritional changes encountered during the transitions in their life cycle. The overall mechanism of glycosome biogenesis is similar to that of peroxisomes in other organisms, but the homologous peroxins involved display low sequence conservation as well as variations in motifs mediating crucial protein-protein interactions in the process. The correct compartmentalisation of enzymes is essential for the regulation of the trypanosomatids' metabolism and consequently for their viability. For Trypanosoma brucei it was shown that glycosomes also play a crucial role in its life-cycle regulation: a crucial developmental control switch involves the translocation of a protein phosphatase from the cytosol into the organelles. Many glycosomal proteins are differentially phosphorylated in different life-cycle stages, possibly indicative of regulation of enzyme activities as an additional means to adapt the metabolic network to the different environmental conditions encountered.
Topics: Animals; Autophagy; Gene Expression Regulation; Glycolysis; Humans; Leishmania; Membrane Proteins; Microbodies; Organelle Biogenesis; Phosphoprotein Phosphatases; Phosphorylation; Protein Isoforms; Protein Transport; Protozoan Proteins; Species Specificity; Trypanosoma
PubMed: 26384872
DOI: 10.1016/j.bbamcr.2015.09.015