scholarly journals The role of the mitochondrial ribosome in human disease: searching for mutations in 12S mitochondrial rRNA with high disruptive potential

2013 ◽  
Vol 23 (4) ◽  
pp. 949-967 ◽  
Author(s):  
Paul M. Smith ◽  
Joanna L. Elson ◽  
Laura C. Greaves ◽  
Saskia B. Wortmann ◽  
Richard J.T. Rodenburg ◽  
...  
Keyword(s):  
Human Disease ◽  
Mitochondrial Rrna ◽  
Mitochondrial Ribosome

scholarly journals Structural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hauke S. Hillen ◽  
Elena Lavdovskaia ◽  
Franziska Nadler ◽  
Elisa Hanitsch ◽  
Andreas Linden ◽  
...  
Keyword(s):  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Ribosomal Subunit ◽  
Structural Basis ◽  
Peptidyl Transferase ◽  
Mitochondrial Ribosomes ◽  
Mitochondrial Ribosome ◽  
In Vitro Reconstitution

AbstractRibosome biogenesis requires auxiliary factors to promote folding and assembly of ribosomal proteins and RNA. Particularly, maturation of the peptidyl transferase center (PTC) is mediated by conserved GTPases, but the molecular basis is poorly understood. Here, we define the mechanism of GTPase-driven maturation of the human mitochondrial large ribosomal subunit (mtLSU) using endogenous complex purification, in vitro reconstitution and cryo-EM. Structures of transient native mtLSU assembly intermediates that accumulate in GTPBP6-deficient cells reveal how the biogenesis factors GTPBP5, MTERF4 and NSUN4 facilitate PTC folding. Addition of recombinant GTPBP6 reconstitutes late mtLSU biogenesis in vitro and shows that GTPBP6 triggers a molecular switch and progression to a near-mature PTC state. Additionally, cryo-EM analysis of GTPBP6-treated mature mitochondrial ribosomes reveals the structural basis for the dual-role of GTPBP6 in ribosome biogenesis and recycling. Together, these results provide a framework for understanding step-wise PTC folding as a critical conserved quality control checkpoint.

scholarly journals Mitochondrial microRNAs: A Putative Role in Tissue Regeneration

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 486
Author(s):  
Sílvia C. Rodrigues ◽  
Renato M. S. Cardoso ◽  
Filipe V. Duarte
Keyword(s):  
Tissue Regeneration ◽  
Protein Complexes ◽  
Mitochondrial Protein ◽  
Noncoding Rnas ◽  
Atp Synthesis ◽  
Mitochondrial Proteins ◽  
Cellular Mechanisms ◽  
Small Noncoding Rnas ◽  
Mitochondrial Ribosome

The most famous role of mitochondria is to generate ATP through oxidative phosphorylation, a metabolic pathway that involves a chain of four protein complexes (the electron transport chain, ETC) that generates a proton-motive force that in turn drives the ATP synthesis by the Complex V (ATP synthase). An impressive number of more than 1000 mitochondrial proteins have been discovered. Since mitochondrial proteins have a dual genetic origin, it is predicted that ~99% of these proteins are nuclear-encoded and are synthesized in the cytoplasmatic compartment, being further imported through mitochondrial membrane transporters. The lasting 1% of mitochondrial proteins are encoded by the mitochondrial genome and synthesized by the mitochondrial ribosome (mitoribosome). As a result, an appropriate regulation of mitochondrial protein synthesis is absolutely required to achieve and maintain normal mitochondrial function. Regarding miRNAs in mitochondria, it is well-recognized nowadays that several cellular mechanisms involving mitochondria are regulated by many genetic players that originate from either nuclear- or mitochondrial-encoded small noncoding RNAs (sncRNAs). Growing evidence collected from whole genome and transcriptome sequencing highlight the role of distinct members of this class, from short interfering RNAs (siRNAs) to miRNAs and long noncoding RNAs (lncRNAs). Some of the mechanisms that have been shown to be modulated are the expression of mitochondrial proteins itself, as well as the more complex coordination of mitochondrial structure and dynamics with its function. We devote particular attention to the role of mitochondrial miRNAs and to their role in the modulation of several molecular processes that could ultimately contribute to tissue regeneration accomplishment.

Role of the NF-kB Pathway in the Pathogenesis of Human Disease States

2001 ◽  
Vol 1 (3) ◽  
pp. 287-296 ◽  
Author(s):  
Yumi Yamamoto ◽  
Richard Gaynor
Keyword(s):  
Human Disease ◽  
Disease States

Exploring the role of non-genetic inheritance in the etiology of human disease

2021 ◽  
Author(s):  
Jill Escher ◽  
Victor Corces ◽  
Isabelle Mansuy ◽  
Wei Yan
Keyword(s):  
Human Disease ◽  
Genetic Inheritance

scholarly journals New molecular and therapeutic insights into canine diffuse large B-cell lymphoma elucidates the role of the dog as a model for human disease

Haematologica ◽  
2018 ◽  
Vol 104 (6) ◽  
pp. e256-e259 ◽  
Author(s):  
Luca Aresu ◽  
Serena Ferraresso ◽  
Laura Marconato ◽  
Luciano Cascione ◽  
Sara Napoli ◽  
...  
Keyword(s):  
B Cell ◽  
Human Disease ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

On the emerging role of rabbit as human disease model and the instrumental role of novel transgenic tools

2012 ◽  
Vol 21 (4) ◽  
pp. 699-713 ◽  
Author(s):  
V. Duranthon ◽  
N. Beaujean ◽  
M. Brunner ◽  
K. E. Odening ◽  
A. Navarrete Santos ◽  
...  
Keyword(s):  
Human Disease ◽  
Disease Model ◽  
Transgenic Tools ◽  
Instrumental Role

An AraC/XylS Family Transcriptional Regulator Modulates the Oxidative Stress Response of Francisella tularensis

2021 ◽  
Author(s):  
Dina Marghani ◽  
Zhuo Ma ◽  
Anthony J. Centone ◽  
Weihua Huang ◽  
Meenakshi Malik ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Francisella Tularensis ◽  
Human Disease ◽  
Transcriptional Regulator ◽  
Intracellular Survival ◽  
Gram Negative ◽  
Expression Of Genes ◽  
Transcription Regulators

Francisella tularensis is a Gram-negative bacterium that causes a fatal human disease known as tularemia. The Centers for Disease Control have classified F. tularensis as Category A Tier-1 Select Agent. The virulence mechanisms of Francisella are not entirely understood. Francisella possesses very few transcription regulators, and most of these regulate the expression of genes involved in intracellular survival and virulence. The F. tularensis genome sequence analysis reveals an AraC ( FTL_ 0689) transcriptional regulator homologous to the AraC/XylS family of transcriptional regulators. In Gram-negative bacteria, AraC activates genes required for L-arabinose utilization and catabolism. The role of the FTL_ 0689 regulator in F. tularensis is not known. In this study, we characterized the role of FTL_ 0689 in gene regulation of F. tularensis and investigated its contribution to intracellular survival and virulence. The results demonstrate that FTL_0689 in Francisella is not required for L-arabinose utilization. Instead, FTL_ 0689 specifically regulates the expression of the oxidative and global stress response, virulence, metabolism, and other key pathways genes required by Francisella when exposed to oxidative stress. The FTL_0689 mutant is attenuated for intramacrophage growth and virulence in mice. Based on the deletion mutant phenotype, FTL_0689 was termed osrR ( o xidative s tress r esponse r egulator). Altogether, this study elucidates the role of the osrR transcriptional regulator in tularemia pathogenesis. IMPORTANCE: The virulence mechanisms of category A select agent Francisella tularensis , the causative agent of a fatal human disease known as tularemia, remain largely undefined. The present study investigated the role of a transcriptional regulator and its overall contribution to the oxidative stress resistance of F. tularensis . The results provide an insight into a novel gene regulatory mechanism, especially when Francisella is exposed to oxidative stress conditions. Understanding such Francisella - specific regulatory mechanisms will identify potential targets for developing effective therapies and vaccines to prevent tularemia.

scholarly journals Caspase-8 mediates inflammation and disease in rodent malaria

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Larissa M. N. Pereira ◽  
Patrícia A. Assis ◽  
Natalia M. de Araújo ◽  
Danielle F. Durso ◽  
Caroline Junqueira ◽  
...  
Keyword(s):  
Septic Shock ◽  
Human Disease ◽  
Caspase 8 ◽  
Inflammasome Activation ◽  
Plasmodium Chabaudi ◽  
Experimental Cerebral Malaria ◽  
Rodent Malaria ◽  
Canonical Pathways ◽  
Inflammatory Caspases

Abstract Earlier studies indicate that either the canonical or non-canonical pathways of inflammasome activation have a limited role on malaria pathogenesis. Here, we report that caspase-8 is a central mediator of systemic inflammation, septic shock in the Plasmodium chabaudi-infected mice and the P. berghei-induced experimental cerebral malaria (ECM). Importantly, our results indicate that the combined deficiencies of caspases-8/1/11 or caspase-8/gasdermin-D (GSDM-D) renders mice impaired to produce both TNFα and IL-1β and highly resistant to lethality in these models, disclosing a complementary, but independent role of caspase-8 and caspases-1/11/GSDM-D in the pathogenesis of malaria. Further, we find that monocytes from malaria patients express active caspases-1, -4 and -8 suggesting that these inflammatory caspases may also play a role in the pathogenesis of human disease.

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