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.

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.

Citation

Ayagama, T., Charles, P. D., Bose, S. J., Boland, B., Priestman, D. A., Aston, D., …Burton, R. A. (2024). Compartmentalization proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation. iScience, 27(6), Article 109609. https://doi.org/10.1016/j.isci.2024.109609

• 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.