Dynamic Regulation of Peroxisomes and Mitochondria during Fungal Development

Raful Navarro-Espíndola; Fernando Suaste-Olmos; Leonardo Peraza-Reyes

doi:10.3390/jof6040302

Dynamic Regulation of Peroxisomes and Mitochondria during Fungal Development

Journal of Fungi ◽

10.3390/jof6040302 ◽

2020 ◽

Vol 6 (4) ◽

pp. 302

Author(s):

Raful Navarro-Espíndola ◽

Fernando Suaste-Olmos ◽

Leonardo Peraza-Reyes

Keyword(s):

Developmental Regulation ◽

Pathogenic Fungi ◽

Mitochondrial Activity ◽

Fungal Development ◽

Developmental Processes ◽

Dynamic Regulation ◽

Dynamic Modulation ◽

Regulatory Systems ◽

Concerted Activity ◽

Organelle Assembly

Peroxisomes and mitochondria are organelles that perform major functions in the cell and whose activity is very closely associated. In fungi, the function of these organelles is critical for many developmental processes. Recent studies have disclosed that, additionally, fungal development comprises a dynamic regulation of the activity of these organelles, which involves a developmental regulation of organelle assembly, as well as a dynamic modulation of the abundance, distribution, and morphology of these organelles. Furthermore, for many of these processes, the dynamics of peroxisomes and mitochondria are governed by common factors. Notably, intense research has revealed that the process that drives the division of mitochondria and peroxisomes contributes to several developmental processes—including the formation of asexual spores, the differentiation of infective structures by pathogenic fungi, and sexual development—and that these processes rely on selective removal of these organelles via autophagy. Furthermore, evidence has been obtained suggesting a coordinated regulation of organelle assembly and dynamics during development and supporting the existence of regulatory systems controlling fungal development in response to mitochondrial activity. Gathered information underscores an important role for mitochondrial and peroxisome dynamics in fungal development and suggests that this process involves the concerted activity of these organelles.

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Mitochondrial Development during Life Cycle Differentiation of African Trypanosomes: Evidence for a Kinetoplast-dependent Differentiation Control Point

Molecular Biology of the Cell ◽

10.1091/mbc.e02-05-0266 ◽

2002 ◽

Vol 13 (10) ◽

pp. 3747-3759 ◽

Cited By ~ 28

Author(s):

Mark W. Timms ◽

Frederick J. van Deursen ◽

Edward F. Hendriks ◽

Keith R. Matthews

Keyword(s):

Life Cycle ◽

Rna Interference ◽

Mitochondrial Genome ◽

Topoisomerase Ii ◽

Developmental Regulation ◽

Control Point ◽

Nuclear Genome ◽

Mitochondrial Activity ◽

African Trypanosomes

Life cycle differentiation of African trypanosomes entails developmental regulation of mitochondrial activity. This requires regulation of the nuclear genome and the kinetoplast, the trypanosome's unusual mitochondrial genome. To investigate the potential cross talk between the nuclear and mitochondrial genome during the events of differentiation, we have 1) disrupted expression of a nuclear-encoded component of the cytochrome oxidase (COX) complex; and 2) generated dyskinetoplastid cells, which lack a mitochondrial genome. Using RNA interference (RNAi) and by disrupting the nuclear COX VI gene, we demonstrate independent regulation of COX component mRNAs encoded in the nucleus and kinetoplast. However, two independent approaches (acriflavine treatment and RNA interference ablation of mitochondrial topoisomerase II) failed to establish clonal lines of dyskinetoplastid bloodstream forms. Nevertheless, dyskinetoplastid forms generated in vivo could undergo two life cycle differentiation events: transition from bloodstream slender to stumpy forms and the initiation of transformation to procyclic forms. However, they subsequently arrested at a specific point in this developmental program before cell cycle reentry. These results provide strong evidence for a requirement for kinetoplast DNA in the bloodstream and for a kinetoplast-dependent control point during differentiation to procyclic forms.

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STRIPAK, a Key Regulator of Fungal Development, Operates as a Multifunctional Signaling Hub

Journal of Fungi ◽

10.3390/jof7060443 ◽

2021 ◽

Vol 7 (6) ◽

pp. 443

Author(s):

Ulrich Kück ◽

Valentina Stein

Keyword(s):

Signaling Pathways ◽

Secondary Metabolism ◽

Fruiting Body ◽

Fruiting Body Formation ◽

Vegetative Development ◽

Fungal Development ◽

Developmental Processes ◽

Structural Investigations ◽

Body Formation ◽

Signaling Complex

The striatin-interacting phosphatases and kinases (STRIPAK) multi subunit complex is a highly conserved signaling complex that controls diverse developmental processes in higher and lower eukaryotes. In this perspective article, we summarize how STRIPAK controls diverse developmental processes in euascomycetes, such as fruiting body formation, cell fusion, sexual and vegetative development, pathogenicity, symbiosis, as well as secondary metabolism. Recent structural investigations revealed information about the assembly and stoichiometry of the complex enabling it to act as a signaling hub. Multiple organellar targeting of STRIPAK subunits suggests how this complex connects several signaling transduction pathways involved in diverse cellular developmental processes. Furthermore, recent phosphoproteomic analysis shows that STRIPAK controls the dephosphorylation of subunits from several signaling complexes. We also refer to recent findings in yeast, where the STRIPAK homologue connects conserved signaling pathways, and based on this we suggest how so far non-characterized proteins may functions as receptors connecting mitophagy with the STRIPAK signaling complex. Such lines of investigation should contribute to the overall mechanistic understanding of how STRIPAK controls development in euascomycetes and beyond.

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Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis

Frontiers in Immunology ◽

10.3389/fimmu.2021.673916 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sally A. Clayton ◽

Lucy MacDonald ◽

Mariola Kurowska-Stolarska ◽

Andrew R. Clark

Keyword(s):

Rheumatoid Arthritis ◽

Genetic Material ◽

Cell Types ◽

Sterile Inflammation ◽

Mitochondrial Activity ◽

Dynamic Regulation ◽

Inflammatory Phenotype ◽

Stress Signals ◽

Molecular Patterns

Mitochondria are major energy-producing organelles that have central roles in cellular metabolism. They also act as important signalling hubs, and their dynamic regulation in response to stress signals helps to dictate the stress response of the cell. Rheumatoid arthritis is an inflammatory and autoimmune disease with high prevalence and complex aetiology. Mitochondrial activity affects differentiation, activation and survival of immune and non-immune cells that contribute to the pathogenesis of this disease. This review outlines what is known about the role of mitochondria in rheumatoid arthritis pathogenesis, and how current and future therapeutic strategies can function through modulation of mitochondrial activity. We also highlight areas of this topic that warrant further study. As producers of energy and of metabolites such as succinate and citrate, mitochondria help to shape the inflammatory phenotype of leukocytes during disease. Mitochondrial components can directly stimulate immune receptors by acting as damage-associated molecular patterns, which could represent an initiating factor for the development of sterile inflammation. Mitochondria are also an important source of intracellular reactive oxygen species, and facilitate the activation of the NLRP3 inflammasome, which produces cytokines linked to disease symptoms in rheumatoid arthritis. The fact that mitochondria contain their own genetic material renders them susceptible to mutation, which can propagate their dysfunction and immunostimulatory potential. Several drugs currently used for the treatment of rheumatoid arthritis regulate mitochondrial function either directly or indirectly. These actions contribute to their immunomodulatory functions, but can also lead to adverse effects. Metabolic and mitochondrial pathways are attractive targets for future anti-rheumatic drugs, however many questions still remain about the precise role of mitochondrial activity in different cell types in rheumatoid arthritis.

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DNA methylation dynamics at transposable elements in mammals

Essays in Biochemistry ◽

10.1042/ebc20190039 ◽

2019 ◽

Vol 63 (6) ◽

pp. 677-689

Author(s):

Natasha Jansz

Keyword(s):

Dna Methylation ◽

Transposable Elements ◽

Transposable Element ◽

Human Development ◽

Developmental Regulation ◽

Repetitive Sequences ◽

Single Copy ◽

Regulatory Sequences ◽

Dynamic Regulation ◽

Element Activity

Abstract Transposable elements dominate the mammalian genome, but their contribution to genetic and epigenetic regulation has been largely overlooked. This was in part due to technical limitations, which made the study of repetitive sequences at single copy resolution difficult. The advancement of next-generation sequencing assays in the last decade has greatly enhanced our understanding of transposable element function. In some instances, specific transposable elements are thought to have been co-opted into regulatory roles during both mouse and human development, while in disease such regulatory potential can contribute to malignancy. DNA methylation is arguably the best characterised regulator of transposable element activity. DNA methylation is associated with transposable element repression, and acts to limit their genotoxic potential. In specific developmental contexts, erasure of DNA methylation is associated with a burst of transposable element expression. Developmental regulation of DNA methylation enables transposon activation, ensuring their survival and propagation throughout the host genome, and also allows the host access to regulatory sequences encoded within the elements. Here I discuss DNA methylation at transposable elements, describing its function and dynamic regulation throughout murine and human development.

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Mitochondrial Activity and Morphology are Affected by Sphinganine in Neurospora Crassa.

Microscopy and Microanalysis ◽

10.1017/s1431927600007236 ◽

1997 ◽

Vol 3 (S2) ◽

pp. 69-70

Author(s):

J. A. Gerlach ◽

K. M. Bart ◽

L. R. Aaronson

Keyword(s):

Neurospora Crassa ◽

Fungal Pathogens ◽

Pathogenic Fungi ◽

Mitochondrial Activity ◽

Transmission Electron Microscopy Analysis ◽

Cell Functions ◽

Transmission Electron ◽

Electron Microscopy Analysis ◽

Microscopy Analysis ◽

Complex Sphingolipids

It has been proposed that sphinganine may function as a natural antifungal barrier in mammals. This sphingoid base is found highly concentrated in epidermis, where it has been documented to inhibit the colonization of pathogenic fungi such as Epidermophyton and Candida. Since Neurospora crassa is sensitive to the effects of sphinganine within the same concentration range as infectious fungi, it is being employed as the model to study the mechanism of sphinganine toxicity in fungal pathogens. With the dramatic increase in fungal mycoses seen in immunocompromised individuals to date, this natural constituent of mammalian epidermis may be employed as a potent, novel antifungal drug.During this project, radioactive labelling with [3H]sphinganine was employed to observe metabolism of exogenous sphinganine into complex sphingolipids. Transmission electron microscopy analysis was utilized to observe changes in cellular ultrastructure, while fluorescence microscopic techniques were used to assay certain cell functions.Within 1 hr, exogenous sources of sphinganine are metabolized into dihydroceramides and cerebrosides by the enzymes of complex sphingolipid synthesis.

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The Small GTPase CsRAC1 Is Important for Fungal Development and Pepper Anthracnose in Colletotrichum scovillei

The Plant Pathology Journal ◽

10.5423/ppj.oa.09.2021.0140 ◽

2021 ◽

Vol 37 (6) ◽

pp. 607-618

Author(s):

Noh-Hyun Lee ◽

Teng Fu ◽

Jong-Hwan Shin ◽

Yong-Won Song ◽

Dong-Cheol Jang ◽

...

Keyword(s):

Rho Gtpase ◽

Fungal Growth ◽

Pathogenic Fungi ◽

Fruit Production ◽

Small Gtpase ◽

Fungal Development ◽

Functional Roles ◽

Pepper Fruit ◽

Colletotrichum Scovillei ◽

Reduced Rate

The pepper anthracnose fungus, Colletotrichum scovillei, causes severe losses of pepper fruit production in the tropical and temperate zones. RAC1 is a highly conserved small GTP-binding protein in the Rho GTPase family. This protein has been demonstrated to play a role in fungal development, and pathogenicity in several plant pathogenic fungi. However, the functional roles of RAC1 are not characterized in C. scovillei causing anthracnose on pepper fruits. Here, we generated a deletion mutant (ΔCsrac1) via homologous recombination to investigate the functional roles of CsRAC1. The ΔCsrac1 showed pleiotropic defects in fungal growth and developments, including vegetative growth, conidiogenesis, conidial germination and appressorium formation, compared to wild-type. Although ΔCsrac1 was able to develop appressoria, it failed to differentiate appressorium pegs. However, ΔCsrac1 still caused anthracnose disease with significantly reduced rate on wounded pepper fruits. Further analyses revealed that ΔCsrac1 was defective in tolerance to oxidative stress and suppression of host-defense genes. Taken together, our results suggest that CsRAC1 plays essential roles in fungal development and pathogenicity in C. scovillei-pepper fruit pathosystem.

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Calcineurin Controls Expression of EAAT1/GLAST in Mouse and Human Cultured Astrocytes through Dynamic Regulation of Protein Synthesis and Degradation

10.20944/preprints202003.0234.v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Giulia Dematteis ◽

Elena Restelli ◽

Roberto Chiesa ◽

Eleonora Aronica ◽

Armando A Genazzani ◽

...

Keyword(s):

Protein Synthesis ◽

Proteasome Inhibitor Mg132 ◽

Dynamic Regulation ◽

Genetic Ablation ◽

Dynamic Modulation ◽

Human Astrocytes ◽

Cultured Astrocytes ◽

Posttranscriptional Level ◽

Protein Synthesis And Degradation ◽

Synthesis And Degradation

Alterations in the expression of glutamate/aspartate transporter (GLAST) have been associated with several neuropathological conditions including Alzheimer’s disease and epilepsy. However, the mechanisms by which GLAST expression is altered are poorly understood. Here we used a combination of pharmacological and genetic approaches coupled with quantitative PCR and Western blot to investigate the mechanism of the regulation of GLAST expression by a Ca2+/calmodulin-activated phosphatase calcineurin (CaN). We show that treatment of cultured hippocampal mouse and fetal human astrocytes with a CaN inhibitor FK506 resulted in a dynamic modulation of GLAST protein expression, being downregulated after 24-48 h, but upregulated after 7 days of continuous FK506 (200 nM) treatment. Protein synthesis, as assessed by puromycin incorporation in neo-synthesized polypeptides, was inhibited already after 1 h of FK506 treatment, while the use of a proteasome inhibitor MG132 (1 μM) shows that GLAST protein degradation was only suppressed after 7 days of FK506 treatment. In astrocytes with constitutive genetic ablation of CaN both protein synthesis and degradation were significantly inhibited. Taken together, our data suggest that, in cultured astrocytes, CaN controls GLAST expression at a posttranscriptional level through regulation of GLAST protein synthesis and degradation.

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Calcineurin Controls Expression of EAAT1/GLAST in Mouse and Human Cultured Astrocytes through Dynamic Regulation of Protein Synthesis and Degradation

International Journal of Molecular Sciences ◽

10.3390/ijms21062213 ◽

2020 ◽

Vol 21 (6) ◽

pp. 2213 ◽

Cited By ~ 1

Author(s):

Giulia Dematteis ◽

Elena Restelli ◽

Roberto Chiesa ◽

Eleonora Aronica ◽

Armando A Genazzani ◽

...

Keyword(s):

Protein Synthesis ◽

Proteasome Inhibitor Mg132 ◽

Dynamic Regulation ◽

Genetic Ablation ◽

Dynamic Modulation ◽

Human Astrocytes ◽

Cultured Astrocytes ◽

Posttranscriptional Level ◽

Protein Synthesis And Degradation ◽

Synthesis And Degradation

Alterations in the expression of glutamate/aspartate transporter (GLAST) have been associated with several neuropathological conditions including Alzheimer’s disease and epilepsy. However, the mechanisms by which GLAST expression is altered are poorly understood. Here we used a combination of pharmacological and genetic approaches coupled with quantitative PCR and Western blot to investigate the mechanism of the regulation of GLAST expression by a Ca2+/calmodulin-activated phosphatase calcineurin (CaN). We show that treatment of cultured hippocampal mouse and fetal human astrocytes with a CaN inhibitor FK506 resulted in a dynamic modulation of GLAST protein expression, being downregulated after 24–48 h, but upregulated after 7 days of continuous FK506 (200 nM) treatment. Protein synthesis, as assessed by puromycin incorporation in neo-synthesized polypeptides, was inhibited already after 1 h of FK506 treatment, while the use of a proteasome inhibitor MG132 (1 μM) shows that GLAST protein degradation was only suppressed after 7 days of FK506 treatment. In astrocytes with constitutive genetic ablation of CaN both protein synthesis and degradation were significantly inhibited. Taken together, our data suggest that, in cultured astrocytes, CaN controls GLAST expression at a posttranscriptional level through regulation of GLAST protein synthesis and degradation.

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The zinc finger proteins ZC3H20 and ZC3H21 stabilise mRNAs encoding membrane proteins and mitochondrial proteins in insect-formTrypanosoma brucei

10.1101/646547 ◽

2019 ◽

Cited By ~ 1

Author(s):

Bin Liu ◽

Kevin Kamanyi Marucha ◽

Christine Clayton

Keyword(s):

Zinc Finger ◽

Developmental Regulation ◽

Specific Protein ◽

Mitochondrial Proteins ◽

Tsetse Flies ◽

Dynamic Regulation ◽

Target Mrnas ◽

Zinc Finger Motifs ◽

Specific Proteins ◽

Stumpy Form

SummaryZC3H20 and ZC3H21 are related trypanosome proteins with two C(x)8C(x)5C(x)3H zinc finger motifs. ZC3H20 is unstable in mammalian-infective bloodstream forms, but becomes more abundant as they transform to growth-arrested stumpy form, while ZC3H21 appears only in the procyclic form of the parasite, which infects Tsetse flies. Each protein binds to several hundred mRNAs, with overlapping but not identical specificities. Both increase expression of bound mRNAs, probably through recruitment of the MKT1-PBP1 complex. At least seventy of the bound mRNAs decrease after RNAi targeting ZC3H20 or ZC3H20 and ZC3H21; their products include procyclic-specific proteins of the plasma membrane and energy metabolism. Simultaneous depletion of ZC3H20 and ZC3H21 causes procyclic forms to shrink and stop growing; in addition to decreases in target mRNAs, there are other changes suggestive of loss of developmental regulation. The bloodstream-form specific protein RBP10 controls ZC3H20 and ZC3H21 expression. Interestingly, some ZC3H20/21 target mRNAs also bind to and are repressed by RBP10, allowing for dynamic regulation as RBP10 decreases and ZC3H20 and ZC3H21 increase during differentiation.

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