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Compartmentalization proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation

Ayagama, Thamali; Charles, Philip D.; Bose, Samuel J.; Boland, Barry; Priestman, David A.; Aston, Daniel; Berridge, Georgina; Fisher, Roman; Cribbs, Adam P.; Song, Qianqian; Mirams, Gary R.; Amponsah, Kwabena; Heather, Lisa; Galione, Antony; Herring, Neil; Kramer, Holger; Capel, Rebecca A.; Platt, Frances M.; Schotten, Ulrich; Verheule, Sander; Burton, Rebecca A.B.

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Authors

Thamali Ayagama

Philip D. Charles

Samuel J. Bose

Barry Boland

David A. Priestman

Daniel Aston

Georgina Berridge

Roman Fisher

Adam P. Cribbs

Qianqian Song

Kwabena Amponsah

Lisa Heather

Antony Galione

Neil Herring

Holger Kramer

Rebecca A. Capel

Frances M. Platt

Ulrich Schotten

Sander Verheule

Rebecca A.B. Burton



Abstract

Endolysosomes (EL) are known for their role in regulating both intracellular trafficking and proteostasis. EL facilitate the elimination of damaged membranes, protein aggregates, membranous organelles and play an important role in calcium signaling. The specific role of EL in cardiac atrial fibrillation (AF) is not well understood. We isolated atrial EL organelles from AF goat biopsies and conducted a comprehensive integrated omics analysis to study the EL-specific proteins and pathways. We also performed electron tomography, protein and enzyme assays on these biopsies. Our results revealed the upregulation of the AMPK pathway and the expression of EL-specific proteins that were not found in whole tissue lysates, including GAA, DYNLRB1, CLTB, SIRT3, CCT2, and muscle-specific HSPB2. We also observed structural anomalies, such as autophagic-vacuole formation, irregularly shaped mitochondria, and glycogen deposition. Our results provide molecular information suggesting EL play a role in AF disease process over extended time frames.

Journal Article Type Article
Acceptance Date Mar 25, 2024
Online Publication Date Mar 28, 2024
Publication Date Jun 21, 2024
Deposit Date Jun 11, 2024
Publicly Available Date Jun 12, 2024
Journal iScience
Electronic ISSN 2589-0042
Publisher Cell Press
Peer Reviewed Peer Reviewed
Volume 27
Issue 6
Article Number 109609
DOI https://doi.org/10.1016/j.isci.2024.109609
Public URL https://nottingham-repository.worktribe.com/output/33282097
Publisher URL https://www.sciencedirect.com/science/article/pii/S2589004224008319
Additional Information This article is maintained by: Elsevier; Article Title: Compartmentalization proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation; Journal Title: iScience; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.isci.2024.109609; Content Type: article; Copyright: © 2024 The Author(s). Published by Elsevier Inc.

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