Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity
Lysosomes are active sites to integrate cellular metabolism and signal transduction. A collection of proteins associated with the lysosome mediate these metabolic and signaling functions. Both lysosomal metabolism and lysosomal signaling have been linked to longevity regulation; however, how lysosom...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2024-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/85214 |
| _version_ | 1797302904004018176 |
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| author | Yong Yu Shihong M Gao Youchen Guan Pei-Wen Hu Qinghao Zhang Jiaming Liu Bentian Jing Qian Zhao David M Sabatini Monther Abu-Remaileh Sung Yun Jung Meng C Wang |
| author_facet | Yong Yu Shihong M Gao Youchen Guan Pei-Wen Hu Qinghao Zhang Jiaming Liu Bentian Jing Qian Zhao David M Sabatini Monther Abu-Remaileh Sung Yun Jung Meng C Wang |
| author_sort | Yong Yu |
| collection | DOAJ |
| description | Lysosomes are active sites to integrate cellular metabolism and signal transduction. A collection of proteins associated with the lysosome mediate these metabolic and signaling functions. Both lysosomal metabolism and lysosomal signaling have been linked to longevity regulation; however, how lysosomes adjust their protein composition to accommodate this regulation remains unclear. Using deep proteomic profiling, we systemically profiled lysosome-associated proteins linked with four different longevity mechanisms. We discovered the lysosomal recruitment of AMP-activated protein kinase and nucleoporin proteins and their requirements for longevity in response to increased lysosomal lipolysis. Through comparative proteomic analyses of lysosomes from different tissues and labeled with different markers, we further elucidated lysosomal heterogeneity across tissues as well as the increased enrichment of the Ragulator complex on Cystinosin-positive lysosomes. Together, this work uncovers lysosomal proteome heterogeneity across multiple scales and provides resources for understanding the contribution of lysosomal protein dynamics to signal transduction, organelle crosstalk, and organism longevity. |
| first_indexed | 2024-03-07T23:44:41Z |
| format | Article |
| id | doaj.art-e0e6d3cb9074413abcb47380357cca41 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-07T23:44:41Z |
| publishDate | 2024-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-e0e6d3cb9074413abcb47380357cca412024-02-19T16:35:10ZengeLife Sciences Publications LtdeLife2050-084X2024-01-011310.7554/eLife.85214Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevityYong Yu0https://orcid.org/0000-0002-9821-9726Shihong M Gao1https://orcid.org/0000-0003-3238-8348Youchen Guan2https://orcid.org/0000-0002-6570-5293Pei-Wen Hu3Qinghao Zhang4Jiaming Liu5Bentian Jing6Qian Zhao7David M Sabatini8Monther Abu-Remaileh9Sung Yun Jung10Meng C Wang11https://orcid.org/0000-0002-5898-6007State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China; Huffington Center on Aging, Baylor College of Medicine, Houston, United StatesDevelopmental Biology Graduate Program, Baylor College of Medicine, Houston, United States; Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United StatesJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States; Molecular and Cellular Biology Graduate Program, Baylor College of Medicine, Houston, United StatesHuffington Center on Aging, Baylor College of Medicine, Houston, United StatesHuffington Center on Aging, Baylor College of Medicine, Houston, United StatesState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, ChinaState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, ChinaJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United StatesInstitute of Organic Chemistry and Biochemistry, Prague, Czech RepublicInstitute for Chemistry, Engineering and Medicine for Human Health (ChEM-H), Stanford University, Stanford, United States; Department of Chemical Engineering and Genetics, Stanford University, Stanford, United StatesDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United StatesHuffington Center on Aging, Baylor College of Medicine, Houston, United States; Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United StatesLysosomes are active sites to integrate cellular metabolism and signal transduction. A collection of proteins associated with the lysosome mediate these metabolic and signaling functions. Both lysosomal metabolism and lysosomal signaling have been linked to longevity regulation; however, how lysosomes adjust their protein composition to accommodate this regulation remains unclear. Using deep proteomic profiling, we systemically profiled lysosome-associated proteins linked with four different longevity mechanisms. We discovered the lysosomal recruitment of AMP-activated protein kinase and nucleoporin proteins and their requirements for longevity in response to increased lysosomal lipolysis. Through comparative proteomic analyses of lysosomes from different tissues and labeled with different markers, we further elucidated lysosomal heterogeneity across tissues as well as the increased enrichment of the Ragulator complex on Cystinosin-positive lysosomes. Together, this work uncovers lysosomal proteome heterogeneity across multiple scales and provides resources for understanding the contribution of lysosomal protein dynamics to signal transduction, organelle crosstalk, and organism longevity.https://elifesciences.org/articles/85214lysosomeaginglongevityAMPKorganelle interaction |
| spellingShingle | Yong Yu Shihong M Gao Youchen Guan Pei-Wen Hu Qinghao Zhang Jiaming Liu Bentian Jing Qian Zhao David M Sabatini Monther Abu-Remaileh Sung Yun Jung Meng C Wang Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity eLife lysosome aging longevity AMPK organelle interaction |
| title | Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity |
| title_full | Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity |
| title_fullStr | Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity |
| title_full_unstemmed | Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity |
| title_short | Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity |
| title_sort | organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity |
| topic | lysosome aging longevity AMPK organelle interaction |
| url | https://elifesciences.org/articles/85214 |
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