scholarly journals CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins

2014 ◽  
Vol 207 (2) ◽  
pp. 213-223 ◽  
Author(s):  
Jie Gao ◽  
Désirée Schatton ◽  
Paola Martinelli ◽  
Henriette Hansen ◽  
David Pla-Martin ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Mitochondrial Proteins ◽  
Control Mechanisms ◽  
Messenger Ribonucleic Acid ◽  
Mrna Binding Protein ◽  
Protein Biogenesis ◽  
Genes Encoding ◽  
Rna Immunoprecipitation ◽  
Tyrosinated Tubulin ◽  
Mrna Binding

Mitochondrial function requires coordination of two genomes for protein biogenesis, efficient quality control mechanisms, and appropriate distribution of the organelles within the cell. How these mechanisms are integrated is currently not understood. Loss of the Clu1/CluA homologue (CLUH) gene led to clustering of the mitochondrial network by an unknown mechanism. We find that CLUH is coregulated both with genes encoding mitochondrial proteins and with genes involved in ribosomal biogenesis and translation. Our functional analysis identifies CLUH as a cytosolic messenger ribonucleic acid (RNA; mRNA)–binding protein. RNA immunoprecipitation experiments followed by next-generation sequencing demonstrated that CLUH specifically binds a subset of mRNAs encoding mitochondrial proteins. CLUH depletion decreased the levels of proteins translated by target transcripts and caused mitochondrial clustering. A fraction of CLUH colocalizes with tyrosinated tubulin and can be detected close to mitochondria, suggesting a role in regulating transport or translation of target transcripts close to mitochondria. Our data unravel a novel mechanism linking mitochondrial biogenesis and distribution.

scholarly journals CREB-1α Is Recruited to and Mediates Upregulation of the Cytochrome c Promoter during Enhanced Mitochondrial Biogenesis Accompanying Skeletal Muscle Differentiation

2008 ◽  
Vol 28 (7) ◽  
pp. 2446-2459 ◽  
Author(s):  
Andras Franko ◽  
Sabine Mayer ◽  
Gerald Thiel ◽  
Ludovic Mercy ◽  
Thierry Arnould ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Critical Role ◽  
Dominant Negative ◽  
Mitochondrial Proteins ◽  
Luciferase Reporter ◽  
Mitochondrial Activity ◽  
Mobility Shift ◽  
Mitochondrial Dna Copy Number ◽  
Genes Encoding ◽  
Phosphorylated Creb

ABSTRACT To further understand pathways coordinating the expression of nuclear genes encoding mitochondrial proteins, we studied mitochondrial biogenesis during differentiation of myoblasts to myotubes. This energy-demanding process was accompanied by a fivefold increase of ATP turnover, covered by an eightfold increase of mitochondrial activity. While no change in mitochondrial DNA copy number was observed, mRNAs as well as proteins for nucleus-encoded cytochrome c, cytochrome c oxidase subunit IV, and mitochondrial transcription factor A (TFAM) increased, together with total cellular RNA and protein levels. Detailed analysis of the cytochrome c promoter by luciferase reporter, binding affinity, and electrophoretic mobility shift assays as well as mutagenesis studies revealed a critical role for cyclic AMP responsive element binding protein 1 (CREB-1) for promoter activation. Expression of two CREB-1 isoforms was observed by using specific antibodies and quantitative reverse transcription-PCR, and a shift from phosphorylated CREB-1Δ in myoblasts to phosphorylated CREB-1α protein in myotubes was shown, while mRNA ratios remained unchanged. Chromatin immunoprecipitation assays confirmed preferential binding of CREB-1α in situ to the cytochrome c promoter in myotubes. Overexpression of constitutively active and dominant-negative forms supported the key role of CREB-1 in regulating the expression of genes encoding mitochondrial proteins during myogenesis and probably also in other situations of enhanced mitochondrial biogenesis.

scholarly journals circRNA N6-methyladenosine methylation in preeclampsia and the potential role of N6-methyladenosine-modified circPAPPA2 in trophoblast invasion

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yonggang Zhang ◽  
Hongling Yang ◽  
Yan Long ◽  
Yipeng Zhang ◽  
Ronggui Chen ◽  
...  
Keyword(s):  
Rna Stability ◽  
Start Codon ◽  
Trophoblast Invasion ◽  
Reverse Transcription Pcr ◽  
Mrna Binding Protein ◽  
Rna Immunoprecipitation ◽  
New Vision ◽  
Mrna Binding

AbstractHere, we performed N6-methyladenosine (m6A) RNA sequencing to determine the circRNA m6A methylation changes in the placentas during the pathogenesis of preeclampsia (PE). We verified the expression of the circRNA circPAPPA2 using quantitative reverse transcription-PCR. An invasion assay was carried out to identify the role of circPAPPA2 in the development of PE. Mechanistically, we investigated the cause of the altered m6A modification of circPAPPA2 through overexpression and knockdown cell experiments, RNA immunoprecipitation, fluorescence in situ hybridization and RNA stability experiments. We found that increases in m6A-modified circRNAs are prevalent in PE placentas and that the main changes in methylation occur in the 3’UTR and near the start codon, implicating the involvement of these changes in PE development. We also found that the levels of circPAPPA2 are decreased but that m6A modification is augmented. Furthermore, we discovered that methyltransferase‑like 14 (METTL14) increases the level of circPAPPA2 m6A methylation and that insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) maintains circPAPPA2 stability. Decreases in IGF2BP3 levels lead to declines in circPAPPA2 levels. In summary, we provide a new vision and strategy for the study of PE pathology and report that placental circRNA m6A modification appears to be an important regulatory mechanism.

scholarly journals Regulation of PPARγCoactivator-1αFunction and Expression in Muscle: Effect of Exercise

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Giulia Uguccioni ◽  
Donna D'souza ◽  
David A. Hood
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Biogenesis ◽  
Posttranslational Modifications ◽  
Mitochondrial Proteins ◽  
Mitochondrial Content ◽  
Brown Adipose ◽  
Muscle Adaptations ◽  
Genes Encoding ◽  
Skeletal Muscle Adaptations

PPARγcoactivator-1α(PGC-1α) is considered to be a major regulator of mitochondrial biogenesis. Though first discovered in brown adipose tissue, this coactivator has emerged as a coordinator of mitochondrial biogenesis in skeletal muscle via enhanced transcription of many nuclear genes encoding mitochondrial proteins. Stimuli such as exercise provoke the activation of signalling cascades that lead to the induction of PGC-1α. Posttranslational modifications also regulate the function of PGC-1α, with a multitude of upstream molecules targeting the protein to modify its activity and/or expression. Previous research has established a positive correlation between resistance to fatigue and skeletal muscle mitochondrial content. Recently, studies have begun to elucidate the specific role of PGC-1αin exercise-related skeletal muscle adaptations, with several studies identifying it as a dominant regulator of organelle synthesis. This paper will highlight the function, regulation, and expression of PGC-1α, as well as the role of the coactivator during exercise adaptations.

scholarly journals Bacteriophages as drivers of bacterial virulence and their potential for biotechnological exploitation

2020 ◽  
Author(s):  
Kaat Schroven ◽  
Abram Aertsen ◽  
Rob Lavigne
Keyword(s):  
Small Molecules ◽  
Bacterial Infections ◽  
Bacterial Virulence ◽  
Arms Race ◽  
Control Mechanisms ◽  
Human Pathogens ◽  
Vaccine Candidates ◽  
Cargo Proteins ◽  
Genes Encoding ◽  
Mutualistic Relationship

ABSTRACT Bacteria-infecting viruses (phages) and their hosts maintain an ancient and complex relationship. Bacterial predation by lytic phages drives an ongoing phage-host arms race, whereas temperate phages initiate mutualistic relationships with their hosts upon lysogenization as prophages. In human pathogens, these prophages impact bacterial virulence in distinct ways: by secretion of phage-encoded toxins, modulation of the bacterial envelope, mediation of bacterial infectivity and the control of bacterial cell regulation. This review builds the argument that virulence-influencing prophages hold extensive, unexplored potential for biotechnology. More specifically, it highlights the development potential of novel therapies against infectious diseases, to address the current antibiotic resistance crisis. First, designer bacteriophages may serve to deliver genes encoding cargo proteins which repress bacterial virulence. Secondly, one may develop small molecules mimicking phage-derived proteins targeting central regulators of bacterial virulence. Thirdly, bacteria equipped with phage-derived synthetic circuits which modulate key virulence factors could serve as vaccine candidates to prevent bacterial infections. The development and exploitation of such antibacterial strategies will depend on the discovery of other prophage-derived, virulence control mechanisms and, more generally, on the dissection of the mutualistic relationship between temperate phages and bacteria, as well as on continuing developments in the synthetic biology field.

scholarly journals Selective packaging of mitochondrial proteins into extracellular vesicles prevents the release of mitochondrial DAMPs

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kiran Todkar ◽  
Lilia Chikhi ◽  
Véronique Desjardins ◽  
Firas El-Mortada ◽  
Geneviève Pépin ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mitochondrial Proteins ◽  
Control Mechanisms ◽  
Mitochondrial Content ◽  
Sorting Nexin ◽  
Inflammatory Conditions ◽  
Selective Targeting ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Insight Into

AbstractMost cells constitutively secrete mitochondrial DNA and proteins in extracellular vesicles (EVs). While EVs are small vesicles that transfer material between cells, Mitochondria-Derived Vesicles (MDVs) carry material specifically between mitochondria and other organelles. Mitochondrial content can enhance inflammation under pro-inflammatory conditions, though its role in the absence of inflammation remains elusive. Here, we demonstrate that cells actively prevent the packaging of pro-inflammatory, oxidized mitochondrial proteins that would act as damage-associated molecular patterns (DAMPs) into EVs. Importantly, we find that the distinction between material to be included into EVs and damaged mitochondrial content to be excluded is dependent on selective targeting to one of two distinct MDV pathways. We show that Optic Atrophy 1 (OPA1) and sorting nexin 9 (Snx9)-dependent MDVs are required to target mitochondrial proteins to EVs, while the Parkinson’s disease-related protein Parkin blocks this process by directing damaged mitochondrial content to lysosomes. Our results provide insight into the interplay between mitochondrial quality control mechanisms and mitochondria-driven immune responses.

scholarly journals Mitochondrien unter Stress: Die Rolle der Präsequenzprotease MPP

BIOspektrum ◽  
2021 ◽  
Vol 27 (4) ◽  
pp. 390-393
Author(s):  
F.-Nora Vögtle
Keyword(s):  
Stress Response ◽  
Cellular Stress ◽  
Critical Role ◽  
Mitochondrial Protein ◽  
Nuclear Genome ◽  
Cellular Stress Response ◽  
Mitochondrial Proteins ◽  
Protein Biogenesis ◽  
Cellular Integrity

AbstractThe majority of mitochondrial proteins are encoded in the nuclear genome, so that the nearly entire proteome is assembled by post-translational preprotein import from the cytosol. Proteomic imbalances are sensed and induce cellular stress response pathways to restore proteostasis. Here, the mitochondrial presequence protease MPP serves as example to illustrate the critical role of mitochondrial protein biogenesis and proteostasis on cellular integrity.

scholarly journals Hypoxia up-regulates the activity of a novel erythropoietin mRNA binding protein.

1991 ◽  
Vol 266 (25) ◽  
pp. 16594-16598
Author(s):  
I.J. Rondon ◽  
L.A. MacMillan ◽  
B.S. Beckman ◽  
M.A. Goldberg ◽  
T. Schneider ◽  
...  
Keyword(s):  
Binding Protein ◽  
Mrna Binding Protein ◽  
Mrna Binding
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