Spermidine and rapamycin reveal distinct autophagy flux response and cargo receptor clearance profile

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dc.contributor.authorDe Wet, Sholtoen_ZA
dc.contributor.authorDu Toit, Andreen_ZA
dc.contributor.authorLoos, Benen_ZA
dc.date.accessioned2023-05-11T12:42:13Z
dc.date.available2023-05-11T12:42:13Z
dc.date.issued2021-01-07
dc.descriptionCITATION: deWet, S.; Du Toit, A.; Loos, B. Spermidine and Rapamycin Reveal Distinct Autophagy Flux Response and Cargo Receptor Clearance Profile. Cells 2021, 10, 95. doi.10.3390/cells10010095en_ZA
dc.descriptionThe original publication is available at: mdpi.comen_ZA
dc.description.abstractAutophagy flux is the rate at which cytoplasmic components are degraded through the entire autophagy pathway and is often measured by monitoring the clearance rate of autophagosomes. The specific means by which autophagy targets specific cargo has recently gained major attention due to the role of autophagy in human pathologies, where specific proteinaceous cargo is insufficiently recruited to the autophagosome compartment, albeit functional autophagy activity. In this context, the dynamic interplay between receptor proteins such as p62/Sequestosome-1 and neighbour of BRCA1 gene 1 (NBR1) has gained attention. However, the extent of receptor protein recruitment and subsequent clearance alongside autophagosomes under different autophagy activities remains unclear. Here, we dissect the concentration-dependent and temporal impact of rapamycin and spermidine exposure on receptor recruitment, clearance and autophagosome turnover over time, employing micropatterning. Our results reveal a distinct autophagy activity response profile, where the extent of autophagosome and receptor co-localisation does not involve the total pool of either entities and does not operate in similar fashion. These results suggest that autophagosome turnover and specific cargo clearance are distinct entities with inherent properties, distinctively contributing towards total functional autophagy activity. These findings are of significance for future studies where disease specific protein aggregates require clearance to preserve cellular proteostasis and viability and highlight the need of discerning and better tuning autophagy machinery activity and cargo clearance.en_ZA
dc.description.versionPublisher’s versionen_ZA
dc.format.extent19 pages : illustrationsen_ZA
dc.identifier.citationde Wet, S.; Du Toit, A.; Loos, B. Spermidine and Rapamycin Reveal Distinct Autophagy Flux Response and Cargo Receptor Clearance Profile. Cells 2021, 10, 95. doi.10.3390/cells10010095en_ZA
dc.identifier.issn2073-4409 (online)en_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/126902
dc.language.isoen_ZAen_ZA
dc.publisherMDPIen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectAutophagy -- Analysisen_ZA
dc.subjectAutophagy fluxen_ZA
dc.subjectCargo receptoren_ZA
dc.subjectCo-localisationen_ZA
dc.subjectSpermidineen_ZA
dc.subjectTurnoveren_ZA
dc.subjectProteins -- Receptorsen_ZA
dc.titleSpermidine and rapamycin reveal distinct autophagy flux response and cargo receptor clearance profileen_ZA
dc.typeArticleen_ZA
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