Biology subjects

Mizunoe, Y.

Publications and source records attributed to Mizunoe, Y..

4 recordsLinked to original sources

bioRxiv2020

Disentangling the biological information encoded in disordered mitochondrial morphology through its rapid elicitation by iCMM

Mitochondrial morphology is dynamically changed in conjunction with spatiotemporal functionality. Although considerable efforts have been made to understand why abnormal mitochondrial morphology occurs in various diseases, the biological significance of mitochondrial morphology in states of health and disease remains to be elucidated owing to technical limitations. In the present study, we developed a novel method, termed inducible Counter Mitochondrial Morphology (iCMM), to purposely manipulate mitochondrial morphological patterns on a minutes timescale, using a chemically inducible dimerization system. Using iCMM, we showed that mitochondrial morphological changes rapidly lead to the characteristic reconstitution of various biological information, which is difficult to investigate by conventional genetic engineering. The manipulation of mitochondrial morphology using iCMM can improve our understanding of the interplay between mitochondrial morphology and cellular functions.Competing Interest StatementThe authors have declared no competing interest.View Full Text

synthetic biology↗

bioRxiv2020

Hierarchical Model for the Role of J-Domain Proteins in Distinct Cellular Functions

In Escherichia coli, the major bacterial Hsp70 system consists of DnaK, three J-domain proteins (JDPs: DnaJ, CbpA, and DjlA), and one nucleotide exchange factor (NEF: GrpE). JDPs determine substrate specificity for the Hsp70 system; however, knowledge on their specific role in bacterial cellular functions is limited. In this study, we demonstrated the role of JDPs in bacterial survival during heat stress and the DnaK-regulated formation of curli--extracellular amyloid fibers involved in E. coli biofilm formation. Genetic analysis with a complete set of JDP-null mutant strains demonstrated that only DnaJ is essential for survival at high temperature, while DnaJ and CbpA are indispensable in DnaK regulation of curli production. Additionally, we found that DnaJ and CbpA are involved in the expression of the master regulator CsgD through the folding of MlrA; this keeps CsgA in a translocation-competent state by preventing its aggregation in the cytoplasm. Our findings support a hierarchical model wherein the role of JDPs in the Hsp70 system differs according to individual cellular functions.

molecular biology↗

bioRxiv2020

Enterohepatic transcription factor CREB3L3 protects atherosclerosis via SREBP competitive inhibition

CREB3L3 is a membrane-bound transcription factor to maintain lipid metabolism in the liver and small intestine. CREB3L3 ablation in Ldlr-/- mice exacerbated hyperlipidemia with remnant ApoB-containing lipoprotein accumulation, developing enhanced aortic atheroma formation, whose extent was additive between liver- and intestine-specific deletion. Conversely, hepatic nuclear CREB3L3 overexpression markedly suppressed atherosclerosis with amelioration of hyperlipidemia. CREB3L3 directly upregulates anti-atherogenic FGF21 and ApoA4, whereas antagonizes hepatic SREBP-mediated lipogenic and cholesterogenic genes and regulates LXR-regulated genes involved in intestinal transport of cholesterol. CREB3L3 deficiency accumulates nuclear SREBP proteins. Because both transcriptional factors share the cleavage system for nuclear transactivation, full-length CREB3L3 and SREBPs on endoplasmic reticulum (ER) functionally inhibit each other. CREB3L3 competitively antagonizes SREBPs for ER-Golgi transport, resulting in ER retention and proteolytic activation inhibition at Golgi, and vice versa. Collectively, due to this new mechanistic interaction between CREB3L3 and SREBPs under atherogenic conditions, CREB3L3 has multi-potent protective effects against atherosclerosis.

physiology↗

bioRxiv2020

A flexible target-specific anti-infection therapeutic platform that can be applied to different microbial species

The emergence of new microbial pathogens, including drug-resistant strains, complicates treatment, thereby threatening global health. We demonstrated a photoimmuno-antimicrobial strategy (PIAS) that eliminated antibody-targets using a photo-activated anti-pathogen antibody generating mechanical stress that damaged the targets binding sites. PIAS is effective against many pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), the fungal pathogen Candida albicans, and viral particles irrespective of their species or drug-resistance status. Animal experiments demonstrated that PIAS saved mice from fatal infections; microbiome and histochemical analyses indicated no apparent effect on normal host microflora and tissues in PIAS-treated mice. Resistance to PIAS was not observed during the eight years of this study. As a new type of anti-infection therapy, PIAS may contribute to advances in anti-infection strategies.

microbiology↗