The close apposition between two different organelles is critical in essential processes such as ion homeostasis, signaling, and lipid transition. However, information related to the structural features of membrane contact sites (MCSs) is limited. This study used immuno-electron microscopy and immuno-electron tomography (I-ET) to analyze the two- and three-dimensional structures of the late endosome-mitochondria contact sites in placental cells. Filamentous structures or tethers were identified that connected the late endosomes and mitochondria. Lamp1 antibody-labeled I-ET revealed enrichment of tethers in the MCSs. The cholesterol-binding endosomal protein metastatic lymph node 64 (MLN64) encoded by STARD3 was required for the formation of this apposition. The distance of the late endosome-mitochondria contact sites was <20 nm, shorter than that in STARD3-knockdown cells (<150 nm). The perturbation of cholesterol egress from the endosomes induced by U18666A treatment produced a longer distance in the contact sites than that in knockdown cells. The late endosome-mitochondria tethers failed to form correctly in STARD3-knockdown cells. Our results unravel the role of MLN64 involved in MCSs between late endosomes and mitochondria in placental cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.yexcr.2023.113668 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Human Interleukin-6 (hIL-6) is a pro inflammatory cytokine that binds to its receptor, IL-6Rα followed by binding to gp130 and subsequent dimerization to form a hexamer signaling complex. A critical inflammation mediator, hIL-6 is associated with a diverse range of diseases and monoclonal antibodies are in clinical use that either target IL-6Rα or hIL-6 to inhibit signaling. Here, we perform high throughput structure-based computational screening using ensemble docking for small molecule antagonists for which the target conformations were taken from 600 ns long molecular dynamics simulations of the apo protein.
View Article and Find Full Text PDFBiomolecular condensates play key roles in the spatiotemporal regulation of cellular processes. Yet, the relationship between atomic features and condensate function remains poorly understood. We studied this relationship using the polar organizing protein Z (PopZ) as a model system, revealing how its material properties and cellular function depend on its ultrastructure.
View Article and Find Full Text PDFClinical and radiographic assessment of effect of platelet-rich fibrin on dental implant osseointegration - A split mouth randomized clinical trial.
J Prosthodont
January 2025
Department of Conservative Dentistry and Endodontics, Sri Ramachandra Dental College and Hospital, Chennai, India.
Purpose: Biomimetic agents are being researched for their potential to stimulate bone formation and boost bone-implant contact. The objective of this study was to assess how osseointegration of dental implants is impacted by platelet-rich fibrin.
Materials And Methods: The present study was a randomized clinical trial with a split mouth design.
Capture, mutual inhibition and release mechanism for aPKC-Par6 and its multisite polarity substrate Lgl.
Nat Struct Mol Biol
January 2025
Signalling and Structural Biology Laboratory, Francis Crick Institute, London, UK.
The mutually antagonistic relationship of atypical protein kinase C (aPKC) and partitioning-defective protein 6 (Par6) with the substrate lethal (2) giant larvae (Lgl) is essential for regulating polarity across many cell types. Although aPKC-Par6 phosphorylates Lgl at three serine sites to exclude it from the apical domain, aPKC-Par6 and Lgl paradoxically form a stable kinase-substrate complex, with conflicting roles proposed for Par6. We report the structure of human aPKCι-Par6α bound to full-length Llgl1, captured through an aPKCι docking site and a Par6 contact.
View Article and Find Full Text PDFMultiple cation insertion into a polyaromatic hydrocarbon guided by data and computation.
Chem Sci
December 2024
Materials Innovation Factory, Department of Chemistry, University of Liverpool 51 Oxford Street L7 3NY Liverpool UK
We report the synthesis, structural characterization and magnetic properties of Kcoronene, and demonstrate a computational screening workflow designed to accelerate the discovery of metal intercalated polycyclic aromatic hydrocarbon (PAH), a class of materials of interest following reports of superconductivity, but lacking demonstrated and understood characterised material compositions. Coronene is identified as a suitable PAH candidate from a library of PAHs for potassium intercalation by computational screening of their electronic structure and of the void space in their crystal structures, targeting LUMO similarity to C and the availability of suitable sites to accommodate inserted cations. Convex hull calculations with energies from crystal structure prediction based on ion insertion into the identified void space of coronene suggest that the = 3 composition in K coronene is stable at 0 K, reinforcing the suitability of coronone for experimental investigation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!