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Lipofuscin Granule Accumulation Requires Autophagy Activation
Lipofuscins are oxidized lipid and protein complexes that accumulate during cellular senescence and tissue aging, regarded as markers for cellular oxidative damage, tissue aging, and certain aging-associated diseases. Therefore, understanding their cellular biological properties is crucial for effec...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Society for Molecular and Cellular Biology
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10440269/ https://www.ncbi.nlm.nih.gov/pubmed/37438887 http://dx.doi.org/10.14348/molcells.2023.0019 |
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author | Song, Seon Beom Shim, Woosung Hwang, Eun Seong |
author_facet | Song, Seon Beom Shim, Woosung Hwang, Eun Seong |
author_sort | Song, Seon Beom |
collection | PubMed |
description | Lipofuscins are oxidized lipid and protein complexes that accumulate during cellular senescence and tissue aging, regarded as markers for cellular oxidative damage, tissue aging, and certain aging-associated diseases. Therefore, understanding their cellular biological properties is crucial for effective treatment development. Through traditional microscopy, lipofuscins are readily observed as fluorescent granules thought to accumulate in lysosomes. However, lipofuscin granule formation and accumulation in senescent cells are poorly understood. Thus, this study examined lipofuscin accumulation in human fibroblasts exposed to various stressors. Our results substantiate that in glucose-starved or replicative senescence cells, where elevated oxidative stress levels activate autophagy, lipofuscins predominately appear as granules that co-localize with autolysosomes due to lysosomal acidity or impairment. Meanwhile, autophagosome formation is attenuated in cells experiencing oxidative stress induced by a doxorubicin pulse and chase, and lipofuscin fluorescence granules seldom manifest in the cytoplasm. As Torin-1 treatment activates autophagy, granular lipofuscins intensify and dominate, indicating that autophagy activation triggers their accumulation. Our results suggest that high oxidative stress activates autophagy but fails in lipofuscin removal, leaving an abundance of lipofuscin-filled impaired autolysosomes, referred to as residual bodies. Therefore, future endeavors in treating lipofuscin pathology-associated diseases and dysfunctions through autophagy activation demand meticulous consideration. |
format | Online Article Text |
id | pubmed-10440269 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Korean Society for Molecular and Cellular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-104402692023-08-22 Lipofuscin Granule Accumulation Requires Autophagy Activation Song, Seon Beom Shim, Woosung Hwang, Eun Seong Mol Cells Research Article Lipofuscins are oxidized lipid and protein complexes that accumulate during cellular senescence and tissue aging, regarded as markers for cellular oxidative damage, tissue aging, and certain aging-associated diseases. Therefore, understanding their cellular biological properties is crucial for effective treatment development. Through traditional microscopy, lipofuscins are readily observed as fluorescent granules thought to accumulate in lysosomes. However, lipofuscin granule formation and accumulation in senescent cells are poorly understood. Thus, this study examined lipofuscin accumulation in human fibroblasts exposed to various stressors. Our results substantiate that in glucose-starved or replicative senescence cells, where elevated oxidative stress levels activate autophagy, lipofuscins predominately appear as granules that co-localize with autolysosomes due to lysosomal acidity or impairment. Meanwhile, autophagosome formation is attenuated in cells experiencing oxidative stress induced by a doxorubicin pulse and chase, and lipofuscin fluorescence granules seldom manifest in the cytoplasm. As Torin-1 treatment activates autophagy, granular lipofuscins intensify and dominate, indicating that autophagy activation triggers their accumulation. Our results suggest that high oxidative stress activates autophagy but fails in lipofuscin removal, leaving an abundance of lipofuscin-filled impaired autolysosomes, referred to as residual bodies. Therefore, future endeavors in treating lipofuscin pathology-associated diseases and dysfunctions through autophagy activation demand meticulous consideration. Korean Society for Molecular and Cellular Biology 2023-08-31 2023-07-13 /pmc/articles/PMC10440269/ /pubmed/37438887 http://dx.doi.org/10.14348/molcells.2023.0019 Text en © The Korean Society for Molecular and Cellular Biology. All rights reserved. https://creativecommons.org/licenses/by-nc-sa/3.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ (https://creativecommons.org/licenses/by-nc-sa/3.0/) |
spellingShingle | Research Article Song, Seon Beom Shim, Woosung Hwang, Eun Seong Lipofuscin Granule Accumulation Requires Autophagy Activation |
title | Lipofuscin Granule Accumulation Requires Autophagy Activation |
title_full | Lipofuscin Granule Accumulation Requires Autophagy Activation |
title_fullStr | Lipofuscin Granule Accumulation Requires Autophagy Activation |
title_full_unstemmed | Lipofuscin Granule Accumulation Requires Autophagy Activation |
title_short | Lipofuscin Granule Accumulation Requires Autophagy Activation |
title_sort | lipofuscin granule accumulation requires autophagy activation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10440269/ https://www.ncbi.nlm.nih.gov/pubmed/37438887 http://dx.doi.org/10.14348/molcells.2023.0019 |
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