Elucidating the Role and Mechanism of Alpha‐Enolase in Senescent Amelioration via Metabolic Reprogramming
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| Format: | Artículo Open Access |
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Wiley
2025
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| author | Yun Haeng Lee Hyunwoong Lim Gyungmin Kim Geonhee Jang Myeong Uk Kuk Ji Ho Park Jee hee Yoon Yoo Jin Lee Duyeol Kim Byeonghyeon So Minseon Kim Hyung Wook Kwon Youngjoo Byun Joon Tae Park |
| author_facet | Yun Haeng Lee Hyunwoong Lim Gyungmin Kim Geonhee Jang Myeong Uk Kuk Ji Ho Park Jee hee Yoon Yoo Jin Lee Duyeol Kim Byeonghyeon So Minseon Kim Hyung Wook Kwon Youngjoo Byun Joon Tae Park Yun Haeng Lee Hyunwoong Lim Gyungmin Kim Geonhee Jang Myeong Uk Kuk Ji Ho Park Jee hee Yoon Yoo Jin Lee Duyeol Kim Byeonghyeon So Minseon Kim Hyung Wook Kwon Youngjoo Byun Joon Tae Park |
| collection | Wiley Open Access |
| contents | Elucidating the Role and Mechanism of Alpha‐Enolase in Senescent Amelioration via Metabolic Reprogramming Yun Haeng Lee Hyunwoong Lim Gyungmin Kim Geonhee Jang Myeong Uk Kuk Ji Ho Park Jee hee Yoon Yoo Jin Lee Duyeol Kim Byeonghyeon So Minseon Kim Hyung Wook Kwon Youngjoo Byun Joon Tae Park Cell Proliferation ABSTRACTSenescent cells are characterised by increased glycolysis dependence. Normalisation of glycolysis metabolism is essential for senescence amelioration. However, the mechanism of proteins involved in cellular glycolysis metabolism has not been fully elucidated. Here, we identified a candidate compound, an oxazole analogue (KB2764), that can improve senescence. To elucidate the mechanism of the KB2764, we investigated the interacting proteins. KB2764 interacted with alpha‐enolase (ENO1) and pyruvate kinase M (PKM), ultimately allowing PKM to phosphorylate ENO1. KB2764 consequently increased mitochondrial ATP production and reduced reliance on glycolysis. Knockdown of the ENO1 experiment in senescent cells demonstrates that regulation of ENO1 activity is a prerequisite for recovery of mitochondrial function. Furthermore, the action of KB2764 extends its application to extend the lifespan of Caenorhabditis elegans. Taken together, our findings reveal a novel mechanism by which senescence is ameliorated through metabolic reprogramming and mitochondrial functional recovery via KB2764‐mediated regulation of ENO1 protein activity. 10.1111/cpr.70049 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1111/cpr.70049 |
| format | Artículo Open Access |
| id | wiley_oa_10_1111_cpr_70049 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Elucidating the Role and Mechanism of Alpha‐Enolase in Senescent Amelioration via Metabolic Reprogramming Yun Haeng Lee Hyunwoong Lim Gyungmin Kim Geonhee Jang Myeong Uk Kuk Ji Ho Park Jee hee Yoon Yoo Jin Lee Duyeol Kim Byeonghyeon So Minseon Kim Hyung Wook Kwon Youngjoo Byun Joon Tae Park Cell Proliferation Elucidating the Role and Mechanism of Alpha‐Enolase in Senescent Amelioration via Metabolic Reprogramming Yun Haeng Lee Hyunwoong Lim Gyungmin Kim Geonhee Jang Myeong Uk Kuk Ji Ho Park Jee hee Yoon Yoo Jin Lee Duyeol Kim Byeonghyeon So Minseon Kim Hyung Wook Kwon Youngjoo Byun Joon Tae Park Cell Proliferation ABSTRACTSenescent cells are characterised by increased glycolysis dependence. Normalisation of glycolysis metabolism is essential for senescence amelioration. However, the mechanism of proteins involved in cellular glycolysis metabolism has not been fully elucidated. Here, we identified a candidate compound, an oxazole analogue (KB2764), that can improve senescence. To elucidate the mechanism of the KB2764, we investigated the interacting proteins. KB2764 interacted with alpha‐enolase (ENO1) and pyruvate kinase M (PKM), ultimately allowing PKM to phosphorylate ENO1. KB2764 consequently increased mitochondrial ATP production and reduced reliance on glycolysis. Knockdown of the ENO1 experiment in senescent cells demonstrates that regulation of ENO1 activity is a prerequisite for recovery of mitochondrial function. Furthermore, the action of KB2764 extends its application to extend the lifespan of Caenorhabditis elegans. Taken together, our findings reveal a novel mechanism by which senescence is ameliorated through metabolic reprogramming and mitochondrial functional recovery via KB2764‐mediated regulation of ENO1 protein activity. 10.1111/cpr.70049 http://creativecommons.org/licenses/by/4.0/ |
| title | Elucidating the Role and Mechanism of Alpha‐Enolase in Senescent Amelioration via Metabolic Reprogramming |
| topic | Cell Proliferation |
| url | https://onlinelibrary.wiley.com/doi/10.1111/cpr.70049 |