Biology subjects

ZHAO, G.

Publications and source records attributed to ZHAO, G..

3 recordsLinked to original sources

bioRxiv2026

Dual role of the OMM E3 Ub ligase MARCH5 in de novo peroxisome biogenesis and mitochondrial quality control through direct regulation of Pex26.

Recent evidence indicates that mitochondria, through the activity of the E3 Ub ligase MARCH5, are critical for de novo peroxisome biogenesis. Here we report that peroxisome biogenesis factor Pex26 is a MARCH5 client protein. In peroxisome-containing cells, MARCH5 interacts with Pex26 and facilitates the transfer of newly synthesized Pex26 from the OMM to peroxisomes. MARCH5 also controls peroxisomal delivery of other candidate peroxins in peroxisome-containing cells. On the other hand, in peroxisome-deficient cells, the turnover rate of Pex26 is dramatically increased, and MARCH5 targets this protein for p97-dependent proteasomal degradation. Both activities are mediated by MARCH5-dependent Pex26 ubiquitination. Knockout of Pex26 induces the accumulation of cells containing Tom20-positive, Catalase-deficient pre-peroxisomes. Further supporting the critical role of MARCH5 in peroxisome biogenesis, these structures are absent in Pex26/MARCH5 double knockout cells. The data support the model, where in peroxisome-containing cells, MARCH5 acts as a peroxisome biogenesis factor, while with defective peroxisome biogenesis, as in Zellweger syndrome cells, it protects mitochondria from potentially toxic accumulation of peroxins on the OMM.

cell biology↗

bioRxiv2025

Pericytes in heart

Pericytes are cells associated primarily with capillaries and are thought to play an important role in the regulation of blood flow. They are often referred to as "mural" cells because they are so frequently found on the exterior walls of small vessels - particularly the capillaries. In heart, high-resolution real-time observations and measurements of pericyte function under physiological conditions are challenging to obtain because of vascular motion, tissue depth and vigorous functional movement. For these reasons, the heart may be one of the most difficult tissues in which to examine pericyte function. Recently, we introduced a perfused papillary muscle preparation (the Z-Prep) that allows us to observe coronary arteries, arterioles, venules, capillaries and myocytes in real time at physiological temperature and pressure while also imaging pericytes 1, 2. Here we present an initial study intended to visualize and characterize quantitatively cardiac pericytes in heart at physiological pressure and temperature conditions. Vascular anatomy was imaged using a z-stack protocol with a rapidly spinning disk confocal microscope. Here the anatomical organization of the pericytes is shown at high resolution with respect to the microcirculation components and cardiac myocytes. The surprising findings include the high abundance of pericytes in native tissue, the extent of their spread on the capillaries themselves, and the existence of major pericyte extensions that travel intimately along the surface of neighboring ventricular myocytes and attach to capillaries on the distant side. These extensions arise from a capillary-based pericyte location and normally end on another capillary endothelial surface and we have named them "bridging" pericytes. Taken together this anatomical organization suggests that the pericytes provide signaling, communication and contractile services to important cellular components of the heart. There is also a provocative suggestion that pericytes in heart are unusually fragile since they suffer an extremely high degree of loss during cellular isolation procedures. However, our investigation of the organization argues against this fragility because of the durability of the dynamic pericyte organization and function despite the stress and brutality of the contracting heart. The work presented here lays the foundation for critical functional studies of pericytes in heart in both health and disease.

physiology↗

bioRxiv2018

The role of two-component system response regulator BceR in antimicrobial resistance, virulence, biofilm formation, and stress response of group B Streptococcus.

The hypervirulent Group B Streptococcus (Streptococcus agalactiae, GBS) serogroup III clonal cluster 17 has been associated with neonatal GBS invasive disease and meningits. Serogroup III, ST283 has recently been implicated in invasive disease among non-pregnant adults in Asia. These strains cluster with strains from freshwater fishes from aquaculture and a foodborne outbreak of sepsis, especially with septic arthritis, had been linked to such consumption in Singapore in 2015. Through comparative genome analyses of invasive and non-invasive strains of ST283, we identified a truncated response regulator gene in the non-invasive strain. This two component response gene, previously named a DNA binding regulator, is conserved among GBS strains and is a homologue of Bacillus subtilis BceR, the response regulator of the BceRSAB system. Loss of function of the BceR response gene in the invasive GBS strain demonstrated bacitracin susceptibility in{Delta} BceR mutant with MICs of 256-fold and four-fold reduction in bacitracin and human cathelicin LL-37 compared to wild type and complementation strains. Upregulation of dltA of wild type strain vs{Delta} BceR mutant was demonstrated (p<0.0001), and was previously shown in Staphylococcus aureus to resist and repel cationic peptides through excess positive charges with D-alanylation of teichoic acids on the cell wall. In addition,{Delta} BceR mutant was less susceptible under oxidative stress under H2O2 stress when compared to wild type strain (p<0.001) and inhibited biofilm formation (p<0.05 and p < 0.0001 for crystal violet staining and cfu counts). The{Delta} BceR mutant also showed reduced mortality as compared to wild type strain (p<0.01) in a murine infection model. Taken together, BceRS is involved in bacitracin and antimicrobial peptide resistance, survival under oxidative stress, biofilm formation and play an important role in the virulence of GBS.\n\nAuthor SummaryTwo-component systems (TCSs) play an important role in virulence in bacteria, and are involved in detecting environmental changes. Although S. agalactiae was reported to contain more predicted TCSs than Streptococcus pneumoniae, few have been studied in detail. In this work, comparative genomic analysis of GBS invasive (hyper-virulent) and non-invasive serotype III-4 strains were performed to determine any gene differences that may account for severity of disease in humans. BceR-like TCS was selected and suspected to be involved in virulence, and thus BceR was deleted in a hyper-virulent GBS serotype III-4 strain. We demonstrated that this BceR-like TCS is involved in GBS virulence and induced proinflammatory host immune responses. Our study of TCS BceR may guide further research into the role of other TCSs in GBS pathogenicity, and further explore therapeutic targets for GBS disease.

microbiology↗