scholarly journals Chloroplast competition is controlled by lipid biosynthesis in evening primroses

2018 ◽  
Author(s):  
Johanna Sobanski ◽  
Patrick Giavalisco ◽  
Axel Fischer ◽  
Julia Kreiner ◽  
Dirk Walther ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Regulatory Region ◽  
Lipid Synthesis ◽  
Nuclear Genome ◽  
Lipid Biosynthesis ◽  
Metabolic Phenotype ◽  
Uniparental Inheritance ◽  
Biparental Inheritance ◽  
Evening Primrose ◽  
Evolutionary Forces

AbstractIn most eukaryotes, organellar genomes are transmitted preferentially by the mother, but molecular mechanisms and evolutionary forces underlying this fundamental biological principle are far from understood. It is believed that biparental inheritance promotes competition between the cytoplasmic organelles and allows the spread of so-called selfish cytoplasmic elements. Those can be, for example, fast replicating or aggressive chloroplasts (plastids) that are incompatible with the hybrid nuclear genome and therefore maladaptive. Here we show that the ability of plastids to compete against each other is a metabolic phenotype determined by extremely rapidly evolving genes in the plastid genome of the evening primroseOenothera. Repeats in the regulatory region ofaccD(the plastid-encoded subunit of the acetyl-CoA carboxylase, which catalyzes the first and rate limiting step of lipid biosynthesis), as well as inycf2(a giant reading frame of still unknown function), are responsible for the differences in competitive behavior of plastid genotypes. Polymorphisms in these genes influence lipid synthesis and most likely profiles of the plastid envelope membrane. These in turn determine plastid division and/or turn-over rates and hence competitiveness. This work uncovers cytoplasmic drive loci controlling the outcome of biparental chloroplast transmission. Here, they define the mode of chloroplast inheritance, since plastid competitiveness can result in uniparental inheritance (through elimination of the “weak” plastid) or biparental inheritance (when two similarly “strong” plastids are transmitted).Significance statementPlastids and mitochondria are usually uniparentally inherited, typically maternally. When the DNA-containing organelles are transmitted to the progeny by both parents, evolutionary theory predicts that the maternal and paternal organelles will compete in the hybrid. As their genomes do not undergo sexual recombination, one organelle will “try” to outcompete the other, thus favoring the evolution and spread of aggressive cytoplasms. The investigations described here in the evening primrose, a model species for biparental plastid transmission, have discovered that chloroplast competition is a metabolic phenotype. It is conferred by rapidly evolving genes that are encoded on the chloroplast genome and control lipid biosynthesis. Due to their high mutation rate these loci can evolve and become fixed in a population very quickly.

scholarly journals Chloroplast competition is controlled by lipid biosynthesis in evening primroses

2019 ◽  
Vol 116 (12) ◽  
pp. 5665-5674 ◽  
Author(s):  
Johanna Sobanski ◽  
Patrick Giavalisco ◽  
Axel Fischer ◽  
Julia M. Kreiner ◽  
Dirk Walther ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Regulatory Region ◽  
Nuclear Genome ◽  
Lipid Biosynthesis ◽  
Metabolic Phenotype ◽  
Uniparental Inheritance ◽  
Biparental Inheritance ◽  
Turnover Rates ◽  
Evening Primrose ◽  
Evolutionary Forces

In most eukaryotes, organellar genomes are transmitted preferentially by the mother, but molecular mechanisms and evolutionary forces underlying this fundamental biological principle are far from understood. It is believed that biparental inheritance promotes competition between the cytoplasmic organelles and allows the spread of so-called selfish cytoplasmic elements. Those can be, for example, fast-replicating or aggressive chloroplasts (plastids) that are incompatible with the hybrid nuclear genome and therefore maladaptive. Here we show that the ability of plastids to compete against each other is a metabolic phenotype determined by extremely rapidly evolving genes in the plastid genome of the evening primroseOenothera. Repeats in the regulatory region ofaccD(the plastid-encoded subunit of the acetyl-CoA carboxylase, which catalyzes the first and rate-limiting step of lipid biosynthesis), as well as inycf2(a giant reading frame of still unknown function), are responsible for the differences in competitive behavior of plastid genotypes. Polymorphisms in these genes influence lipid synthesis and most likely profiles of the plastid envelope membrane. These in turn determine plastid division and/or turnover rates and hence competitiveness. This work uncovers cytoplasmic drive loci controlling the outcome of biparental chloroplast transmission. Here, they define the mode of chloroplast inheritance, as plastid competitiveness can result in uniparental inheritance (through elimination of the “weak” plastid) or biparental inheritance (when two similarly “strong” plastids are transmitted).

scholarly journals Enhanced lipid biosynthesis in human tumor-induced macrophages contributes to their protumoral characteristics

2020 ◽  
Vol 8 (2) ◽  
pp. e000638 ◽  
Author(s):  
Katrin Rabold ◽  
Anna Aschenbrenner ◽  
Christoph Thiele ◽  
Collins K Boahen ◽  
Alexander Schiltmans ◽  
...  
Keyword(s):  
Lipid Synthesis ◽  
Human Tumor ◽  
Total Lipid Content ◽  
Lipid Biosynthesis ◽  
Metabolic Phenotype ◽  
Metabolic Shift ◽  
Metabolome Analysis ◽  
Intracellular Lipids ◽  
Lipidome Analysis ◽  
And Function

BackgroundTumor-associated macrophages (TAMs) are key components of the tumor microenvironment (TME) in non-medullary thyroid carcinoma (TC) and neuroblastoma (NB), being associated with a poor prognosis for patients. However, little is known about how tumors steer the specific metabolic phenotype and function of TAMs.MethodsIn a human coculture model, transcriptome, metabolome and lipidome analysis were performed on TC-induced and NB-induced macrophages. The metabolic shift was correlated to functional readouts, such as cytokine production and reactive oxygen species (ROS) production, including pharmacological inhibition of metabolic pathways.ResultsBased on transcriptome and metabolome analysis, we observed a strong upregulation of lipid biosynthesis pathways in TAMs. Subsequently, lipidome analysis revealed that tumor-induced macrophages have an increased total lipid content and enriched levels of intracellular lipids, especially phosphoglycerides and sphingomyelins. Strikingly, this metabolic shift in lipid synthesis contributes to their protumoral functional characteristics: blocking key enzymes of lipid biosynthesis in the tumor-induced macrophages reversed the increased inflammatory cytokines and the capacity to produce ROS, two well-known protumoral factors in the TME.ConclusionsTaken together, our data show that tumor cells can stimulate lipid biosynthesis in macrophages to induce protumoral cytokine and ROS responses and advocate lipid biosynthesis as a potential therapeutic target to reprogram the TME.

scholarly journals Atypical mitochondrial inheritance patterns in eukaryotes

Genome ◽  
2015 ◽  
Vol 58 (10) ◽  
pp. 423-431 ◽  
Author(s):  
Sophie Breton ◽  
Donald T. Stewart
Keyword(s):  
Sex Determination ◽  
Molecular Mechanisms ◽  
Maternal Inheritance ◽  
Uniparental Inheritance ◽  
Mitochondrial Inheritance ◽  
Doubly Uniparental Inheritance ◽  
Inheritance Patterns ◽  
Sexual Systems ◽  
Evolutionary Forces ◽  
Mtdna Inheritance

Mitochondrial DNA (mtDNA) is predominantly maternally inherited in eukaryotes. Diverse molecular mechanisms underlying the phenomenon of strict maternal inheritance (SMI) of mtDNA have been described, but the evolutionary forces responsible for its predominance in eukaryotes remain to be elucidated. Exceptions to SMI have been reported in diverse eukaryotic taxa, leading to the prediction that several distinct molecular mechanisms controlling mtDNA transmission are present among the eukaryotes. We propose that these mechanisms will be better understood by studying the deviations from the predominating pattern of SMI. This minireview summarizes studies on eukaryote species with unusual or rare mitochondrial inheritance patterns, i.e., other than the predominant SMI pattern, such as maternal inheritance of stable heteroplasmy, paternal leakage of mtDNA, biparental and strictly paternal inheritance, and doubly uniparental inheritance of mtDNA. The potential genes and mechanisms involved in controlling mitochondrial inheritance in these organisms are discussed. The linkage between mitochondrial inheritance and sex determination is also discussed, given that the atypical systems of mtDNA inheritance examined in this minireview are frequently found in organisms with uncommon sexual systems such as gynodioecy, monoecy, or andromonoecy. The potential of deviations from SMI for facilitating a better understanding of a number of fundamental questions in biology, such as the evolution of mtDNA inheritance, the coevolution of nuclear and mitochondrial genomes, and, perhaps, the role of mitochondria in sex determination, is considerable.

scholarly journals A Concerted Action of UBA5 C-Terminal Unstructured Regions Is Important for Transfer of Activated UFM1 to UFC1

2021 ◽  
Vol 22 (14) ◽  
pp. 7390
Author(s):  
Nicole Wesch ◽  
Frank Löhr ◽  
Natalia Rogova ◽  
Volker Dötsch ◽  
Vladimir V. Rogov
Keyword(s):  
Cellular Localization ◽  
Molecular Mechanisms ◽  
Biochemical Characterization ◽  
Effective Interaction ◽  
Regulatory Region ◽  
Titration Calorimetry ◽  
Enzymatic Reactions ◽  
Cellular Processes ◽  
Mechanism Of Interaction

Ubiquitin fold modifier 1 (UFM1) is a member of the ubiquitin-like protein family. UFM1 undergoes a cascade of enzymatic reactions including activation by UBA5 (E1), transfer to UFC1 (E2) and selective conjugation to a number of target proteins via UFL1 (E3) enzymes. Despite the importance of ufmylation in a variety of cellular processes and its role in the pathogenicity of many human diseases, the molecular mechanisms of the ufmylation cascade remains unclear. In this study we focused on the biophysical and biochemical characterization of the interaction between UBA5 and UFC1. We explored the hypothesis that the unstructured C-terminal region of UBA5 serves as a regulatory region, controlling cellular localization of the elements of the ufmylation cascade and effective interaction between them. We found that the last 20 residues in UBA5 are pivotal for binding to UFC1 and can accelerate the transfer of UFM1 to UFC1. We solved the structure of a complex of UFC1 and a peptide spanning the last 20 residues of UBA5 by NMR spectroscopy. This structure in combination with additional NMR titration and isothermal titration calorimetry experiments revealed the mechanism of interaction and confirmed the importance of the C-terminal unstructured region in UBA5 for the ufmylation cascade.

scholarly journals Interaction of CREB and PGC-1α Induces Fibronectin Type III Domain-Containing Protein 5 Expression in C2C12 Myotubes

2018 ◽  
Vol 50 (4) ◽  
pp. 1574-1584 ◽  
Author(s):  
Xiu-ying Yang ◽  
Margaret C.L. Tse ◽  
Xiang Hu ◽  
Wei-hua Jia ◽  
Guan-hua Du ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Metabolic Effects ◽  
Hek293 Cells ◽  
Metabolic Phenotype ◽  
C2c12 Myotubes ◽  
Type Iii ◽  
Fibronectin Type Iii ◽  
Fibronectin Type Iii Domain ◽  
Fibronectin Type

Background/Aims: Fibronectin type III domain-containing protein 5 (FNDC5), also known as irisin, is a myokine secreted from muscle in response to exercise. However, the molecular mechanisms that regulate FNDC5 expression and the functional significance of irisn in skeletal muscle remain unknown. In this study, we explored the potential pathways that induce FNDC5 expression and delineated the metabolic effects of irisin on skeletal muscle. Methods: C2C12 myotubes were treated with drugs at various concentrations and durations. The expression and activation of genes were measured by real-time polymerase chain reaction (qRT-PCR) and Western blotting. Oxidative phosphorylation was quantified by measuring the oxygen consumption rate (OCR). Results: We found that the exercise-mimicking treatment (cAMP, forskolin and isoproterenol) increased Fndc5 expression in C2C12 myotubes. CREB over-expressed C2C12 myotubes displayed higher Fndc5 expression. CREB over-expression also promoted peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) expression. PGC-1α-induced Fndc5 expression was blocked when the dominant negative form of CREB (S133A) was present. PGC-1α mutation (S570A) also decreased Fndc5 expression. Immunoprecipitation showed that overexpressed PGC-1α complexed with CREB in HEK293 cells. C2C12 myotubes treated with forskolin also increased endogenous CREB and PGC-1α binding. Functionally, irisin treatment increased mitochondrial respiration, enhanced ATP production, promoted fatty acid oxidation but decreased glycolysis in myotubes. Conclusion: Our observation indicates that cAMP-mediated PGC-1α/CREB interaction triggers Fndc5 expression, which acts as an autocrine/paracrine to shape the metabolic phenotype of myotubes.

scholarly journals A Genetic Screen for Mycobacterium tuberculosis Mutants Defective for Phagosome Maturation Arrest Identifies Components of the ESX-1 Secretion System

2007 ◽  
Vol 75 (6) ◽  
pp. 2668-2678 ◽  
Author(s):  
Jason A. MacGurn ◽  
Jeffery S. Cox
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Molecular Mechanisms ◽  
Lipid Synthesis ◽  
Secretion System ◽  
Growth Defect ◽  
Phagosome Maturation ◽  
Macrophage Infection ◽  
Maturation Arrest ◽  
System A ◽  
Early Endosomes

ABSTRACT After phagocytosis, the intracellular pathogen Mycobacterium tuberculosis arrests the progression of the nascent phagosome into a phagolysosome, allowing for replication in a compartment that resembles early endosomes. To better understand the molecular mechanisms that govern phagosome maturation arrest, we performed a visual screen on a set of M. tuberculosis mutants specifically attenuated for growth in mice to identify strains that failed to arrest phagosome maturation and trafficked to late phagosomal compartments. We identified 10 such mutants that could be partitioned into two classes based on the kinetics of trafficking. Importantly, four of these mutants harbor mutations in genes that encode components of the ESX-1 secretion system, a pathway critical for M. tuberculosis virulence. Although ESX-1 is required, the known ESX-1 secreted proteins are dispensable for phagosome maturation arrest, suggesting that a novel effector required for phagosome maturation arrest is secreted by ESX-1. Other mutants identified in this screen had mutations in genes involved in lipid synthesis and secretion and in molybdopterin biosynthesis, as well as in genes with unknown functions. Most of these trafficking mutants exhibited a corresponding growth defect during macrophage infection, but two mutants grew like wild-type M. tuberculosis during macrophage infection. Our results support the emerging consensus that multiple factors from M. tuberculosis, including the ESX-1 secretion system, are involved in modulating trafficking within the host.

scholarly journals Transcription of the Human 5-Hydroxytryptamine Receptor 2B (HTR2B) Gene Is under the Regulatory Influence of the Transcription Factors NFI and RUNX1 in Human Uveal Melanoma

2018 ◽  
Vol 19 (10) ◽  
pp. 3272 ◽  
Author(s):  
Manel Benhassine ◽  
Sylvain Guérin
Keyword(s):  
Transcription Factors ◽  
Uveal Melanoma ◽  
Serotonin Receptor ◽  
Molecular Mechanisms ◽  
Regulatory Region ◽  
Gene Signature ◽  
Regulatory Elements ◽  
Gene Encoding ◽  
Aberrant Expression ◽  
Factor I

Because it accounts for 70% of all eye cancers, uveal melanoma (UM) is therefore the most common primary ocular malignancy. In this study, we investigated the molecular mechanisms leading to the aberrant expression of the gene encoding the serotonin receptor 2B (HTR2B), one of the most discriminating among the candidates from the class II gene signature, in metastatic and non-metastatic UM cell lines. Transfection analyses revealed that the upstream regulatory region of the HTR2B gene contains a combination of alternative positive and negative regulatory elements functional in HTR2B− but not in HTR23B+ UM cells. We demonstrated that both the transcription factors nuclear factor I (NFI) and Runt-related transcription factor I (RUNX1) interact with regulatory elements from the HTR2B gene to either activate (NFI) or repress (RUNX1) HTR2B expression in UM cells. The results of this study will help understand better the molecular mechanisms accounting for the abnormal expression of the HTR2B gene in uveal melanoma.

scholarly journals Comparative transcriptomics of a monocotyledonous geophyte reveals shared molecular mechanisms of underground storage organ formation

2019 ◽  
Author(s):  
Carrie M. Tribble ◽  
Jesús Martínez-Gómez ◽  
Fernando Alzate-Guarin ◽  
Carl J. Rothfels ◽  
Chelsea D. Specht
Keyword(s):  
Molecular Mechanisms ◽  
Vascular Plant ◽  
Gene Tree ◽  
Comparative Transcriptomics ◽  
Differentially Expressed ◽  
Underground Storage ◽  
Cell Wall Modification ◽  
Evolutionary Forces ◽  
Tuberous Roots ◽  
Root Tuber

AbstractMany species from across the vascular plant tree-of-life have modified standard plant tissues into tubers, bulbs, corms, and other underground storage organs (USOs), unique innovations which allow these plants to retreat underground. Our ability to understand the developmental and evolutionary forces that shape these morphologies is limited by a lack of studies on certain USOs and plant clades. Bomarea multiflora (Alstroemeriaceae) is a monocot with tuberous roots, filling a key gap in our understanding of USO development. We take a comparative transcriptomics approach to characterizing the molecular mechanisms of tuberous root formation in B. multiflora and compare these mechanisms to those identified in other USOs across diverse plant lineages. We sequenced transcriptomes from the growing tip of four tissue types (aerial shoot, rhizome, fibrous root, and root tuber) of three individuals of B. multiflora. We identify differentially expressed isoforms between tuberous and non-tuberous roots and test the expression of a priori candidate genes implicated in underground storage in other taxa. We identify 271 genes that are differentially expressed in root tubers versus non-tuberous roots, including genes implicated in cell wall modification, defense response, and starch biosynthesis. We also identify a phosphatidylethanolamine-binding protein (PEBP), which has been implicated in tuberization signalling in other taxa and, through gene-tree analysis, place this copy in a phylogenytic context. These findings suggest that some similar molecular processes underlie the formation of underground storage structures across flowering plants despite the long evolutionary distances among taxa and non-homologous morphologies (e.g., bulbs versus tubers).

scholarly journals SCAP/SREBPs are Central Players in Lipid Metabolism and Novel Metabolic Targets in Cancer Therapy

2018 ◽  
Vol 18 (6) ◽  
pp. 484-493 ◽  
Author(s):  
Xiang Cheng ◽  
Jianying Li ◽  
Deliang Guo
Keyword(s):  
Lipid Metabolism ◽  
Cancer Therapy ◽  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Regulatory Element ◽  
Lipid Synthesis ◽  
Feedback Regulation ◽  
Negative Feedback Regulation ◽  
Expression Of Genes ◽  
New Findings

Lipid metabolism reprogramming emerges as a new hallmark of malignancies. Sterol regulatory element-binding proteins (SREBPs), which are central players in lipid metabolism, are endoplasmic reticulum (ER)-bound transcription factors that control the expression of genes important for lipid synthesis and uptake. Their transcriptional activation requires binding to SREBP cleavageactivating protein (SCAP) to translocate their inactive precursors from the ER to the Golgi to undergo cleavage and subsequent nucleus translocation of their NH2-terminal forms. Recent studies have revealed that SREBPs are markedly upregulated in human cancers, providing the mechanistic link between lipid metabolism alterations and malignancies. Pharmacological or genetic inhibition of SCAP or SREBPs significantly suppresses tumor growth in various cancer models, demonstrating that SCAP/SREBPs could serve as promising metabolic targets for cancer therapy. In this review, we will summarize recent progress in our understanding of the underlying molecular mechanisms regulating SCAP/SREBPs and lipid metabolism in malignancies, discuss new findings about SREBP trafficking, which requires SCAP N-glycosylation, and introduce a newly identified microRNA-29-mediated negative feedback regulation of the SCAP/SREBP pathway. Moreover, we will review recently developed inhibitors targeting the SCAP/SREBP pathway for cancer treatment.

scholarly journals Import of Non-Coding RNAs into Human Mitochondria: A Critical Review and Emerging Approaches

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 286 ◽  
Author(s):  
Damien Jeandard ◽  
Anna Smirnova ◽  
Ivan Tarassov ◽  
Eric Barrey ◽  
Alexandre Smirnov ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Nuclear Genome ◽  
Genetic System ◽  
Mitochondrial Import ◽  
In Situ Techniques ◽  
Genome Wide ◽  
Experimental Approaches ◽  
Non Coding Rnas ◽  
Analyze Data

Mitochondria harbor their own genetic system, yet critically depend on the import of a number of nuclear-encoded macromolecules to ensure their expression. In all eukaryotes, selected non-coding RNAs produced from the nuclear genome are partially redirected into the mitochondria, where they participate in gene expression. Therefore, the mitochondrial RNome represents an intricate mixture of the intrinsic transcriptome and the extrinsic RNA importome. In this review, we summarize and critically analyze data on the nuclear-encoded transcripts detected in human mitochondria and outline the proposed molecular mechanisms of their mitochondrial import. Special attention is given to the various experimental approaches used to study the mitochondrial RNome, including some recently developed genome-wide and in situ techniques.

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