Yusuke Sekine
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View article: Inhibition of virally induced TFEB proteasomal degradation as a host-centric therapeutic approach for coronaviral infection
Inhibition of virally induced TFEB proteasomal degradation as a host-centric therapeutic approach for coronaviral infection Open
The endolysosomal pathway plays an evolutionarily conserved role in pathogen clearance, and viruses have evolved complex mechanisms to evade this host defense system. Here, we describe a previously unidentified aspect of coronaviral infect…
View article: OMA1 clears traffic jam in TOM tunnel in mammals
OMA1 clears traffic jam in TOM tunnel in mammals Open
Using an engineered mitochondrial clogger, Krakowczyk et al. (https://doi.org/10.1083/jcb.202306051) identified the OMA1 protease as a critical component that eliminates import failure at the TOM translocase in mammalian cells, providing a…
View article: A mitochondrial iron-responsive pathway regulated by DELE1
A mitochondrial iron-responsive pathway regulated by DELE1 Open
View article: A mitochondrial iron-sensing pathway regulated by DELE1
A mitochondrial iron-sensing pathway regulated by DELE1 Open
Summary The heme-regulated kinase HRI is activated under heme/iron deficient conditions; however, the underlying molecular mechanism is incompletely understood. Here, we show that iron deficiency-induced HRI activation involves a heme-inde…
View article: Discovery of bactericides as an acute mitochondrial membrane damage inducer
Discovery of bactericides as an acute mitochondrial membrane damage inducer Open
Discovery of alexidine and chlorhexidine as small molecules to acutely and preferentially perturb the mitochondrial membrane architecture in the inner mitochondrial membrane, providing a unique chemical-biological tool for delineating mito…
View article: Modulation of lysosomal function as a therapeutic approach for coronaviral infections
Modulation of lysosomal function as a therapeutic approach for coronaviral infections Open
The endo-lysosomal pathway plays an important role in pathogen clearance and both bacteria and viruses have evolved complex mechanisms to evade this host system. Here, we describe a novel aspect of coronaviral infection, whereby the master…
View article: Discovery of bactericides as an acute mitochondrial membrane damage inducer
Discovery of bactericides as an acute mitochondrial membrane damage inducer Open
Mitochondria evolved from endosymbiotic bacteria to become essential organelles of eukaryotic cells. The defined lipid composition and structure of mitochondrial membranes are critical for the proper functioning of mitochondria. However, m…
View article: Acetylation-mediated remodeling of the nucleolus regulates cellular acetyl-CoA responses
Acetylation-mediated remodeling of the nucleolus regulates cellular acetyl-CoA responses Open
The metabolite acetyl-coenzyme A (acetyl-CoA) serves as an essential element for a wide range of cellular functions including adenosine triphosphate (ATP) production, lipid synthesis, and protein acetylation. Intracellular acetyl-CoA conce…
View article: Hyperlipidaemia and IFNgamma/TNFalpha Synergism are associated with cholesterol crystal formation in Endothelial cells partly through modulation of Lysosomal pH and Cholesterol homeostasis
Hyperlipidaemia and IFNgamma/TNFalpha Synergism are associated with cholesterol crystal formation in Endothelial cells partly through modulation of Lysosomal pH and Cholesterol homeostasis Open
Funding was provided by the Intramural Research Program at NIH (NNM) and the National Psoriasis Foundation (NNM and YB).
View article: Sequential CRISPR-Based Screens Identify LITAF and CDIP1 as the Bacillus cereus Hemolysin BL Toxin Host Receptors
Sequential CRISPR-Based Screens Identify LITAF and CDIP1 as the Bacillus cereus Hemolysin BL Toxin Host Receptors Open
View article: The coupling of translational control and stress responses
The coupling of translational control and stress responses Open
The translation of messenger RNA (mRNA) into protein is a multistep process by which genetic information transcribed into an mRNA is decoded to produce a specific polypeptide chain of amino acids. Ribosomes play a central role in translati…
View article: Acetylation-mediated phase control of the nucleolus regulates cellular acetyl-CoA responses
Acetylation-mediated phase control of the nucleolus regulates cellular acetyl-CoA responses Open
Summary The metabolite acetyl-CoA serves as an essential element for a wide range of cellular functions including ATP production, lipid synthesis and protein acetylation. Intracellular acetyl-CoA concentrations are associated with nutrient…
View article: Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B
Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B Open
ISRIB mechanism of action In rodents, a druglike small molecule named ISRIB enhances cognition and reverses cognitive deficits after traumatic brain injury. ISRIB activates a protein complex called eIF2B that is required for the synthesis …
View article: Paradoxical Sensitivity to an Integrated Stress Response Blocking Mutation in Vanishing White Matter Cells
Paradoxical Sensitivity to an Integrated Stress Response Blocking Mutation in Vanishing White Matter Cells Open
The eukaryotic translation initiation factor eIF2B promotes mRNA translation as a guanine nucleotide exchange factor (GEF) for translation initiation factor 2 (eIF2). Endoplasmic reticulum (ER) stress-mediated activation of the kinase PERK…
View article: KLHDC10 Deficiency Protects Mice against TNFα-Induced Systemic Inflammation
KLHDC10 Deficiency Protects Mice against TNFα-Induced Systemic Inflammation Open
Systemic inflammatory response syndrome (SIRS) is a form of fatal acute inflammation for which there is no effective treatment. Here, we revealed that the ablation of Kelch domain containing 10 (KLHDC10), which we had originally identified…
View article: Mutations in a translation initiation factor identify the target of a memory-enhancing compound
Mutations in a translation initiation factor identify the target of a memory-enhancing compound Open
Identification of a memory drug target ISRIB is a potent inhibitor of the integrated stress response (ISR), which involves the activation of eIF2α-specific kinases, phosphorylation of eIF2α, and consequent down-regulation of global transla…
View article: Apoptosis Signal-regulating Kinase 1 (ASK1)-p38 Pathway-dependent Cytoplasmic Translocation of the Orphan Nuclear Receptor NR4A2 Is Required for Oxidative Stress-induced Necrosis
Apoptosis Signal-regulating Kinase 1 (ASK1)-p38 Pathway-dependent Cytoplasmic Translocation of the Orphan Nuclear Receptor NR4A2 Is Required for Oxidative Stress-induced Necrosis Open
View article: Partial restoration of protein synthesis rates by the small molecule ISRIB prevents neurodegeneration without pancreatic toxicity
Partial restoration of protein synthesis rates by the small molecule ISRIB prevents neurodegeneration without pancreatic toxicity Open