Restoring calcium crosstalk between ER and mitochondria promotes intestinal stem cell rejuvenation through autophagy in aged Drosophila
Abstract Breakdown of calcium network is closely associated with cellular aging. Previously, we found that cytosolic calcium (CytoCa2+) levels were elevated while mitochondrial calcium (MitoCa2+) levels were decreased and associated with metabolic shift in aged intestinal stem cells (ISCs) of Drosop...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-05-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60196-4 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850231377084022784 |
|---|---|
| author | Yao Zhang Peng Ma Saifei Wang Shuxin Chen Hansong Deng |
| author_facet | Yao Zhang Peng Ma Saifei Wang Shuxin Chen Hansong Deng |
| author_sort | Yao Zhang |
| collection | DOAJ |
| description | Abstract Breakdown of calcium network is closely associated with cellular aging. Previously, we found that cytosolic calcium (CytoCa2+) levels were elevated while mitochondrial calcium (MitoCa2+) levels were decreased and associated with metabolic shift in aged intestinal stem cells (ISCs) of Drosophila. How MitoCa2+ was decoupled from the intracellular calcium network and whether the reduction of MitoCa2+ drives ISC aging, however, remains unresolved. Here, we show that genetically restoring MitoCa2+ can reverse ISC functional decline and promote intestinal homeostasis by activating autophagy in aged flies. Further studies indicate that MitoCa2+ and Mitochondria–ER contacts (MERCs) form a positive feedback loop via IP3R to regulate autophagy independent of AMPK. Breakdown of this loop is responsible for MitoCa2+ reduction and ISC dysfunction in aged flies. Our results identify a regulatory module for autophagy initiation involving calcium crosstalk between the ER and mitochondria, providing a strategy to treat aging and age-related diseases. |
| format | Article |
| id | doaj-art-b4d67420dd914a7ebbd5176c1c87f24d |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b4d67420dd914a7ebbd5176c1c87f24d2025-08-20T02:03:32ZengNature PortfolioNature Communications2041-17232025-05-0116111710.1038/s41467-025-60196-4Restoring calcium crosstalk between ER and mitochondria promotes intestinal stem cell rejuvenation through autophagy in aged DrosophilaYao Zhang0Peng Ma1Saifei Wang2Shuxin Chen3Hansong Deng4Yangzhi Rehabilitation Hospital, Sunshine Rehabilitation Center, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityYangzhi Rehabilitation Hospital, Sunshine Rehabilitation Center, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityYangzhi Rehabilitation Hospital, Sunshine Rehabilitation Center, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityYangzhi Rehabilitation Hospital, Sunshine Rehabilitation Center, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityYangzhi Rehabilitation Hospital, Sunshine Rehabilitation Center, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityAbstract Breakdown of calcium network is closely associated with cellular aging. Previously, we found that cytosolic calcium (CytoCa2+) levels were elevated while mitochondrial calcium (MitoCa2+) levels were decreased and associated with metabolic shift in aged intestinal stem cells (ISCs) of Drosophila. How MitoCa2+ was decoupled from the intracellular calcium network and whether the reduction of MitoCa2+ drives ISC aging, however, remains unresolved. Here, we show that genetically restoring MitoCa2+ can reverse ISC functional decline and promote intestinal homeostasis by activating autophagy in aged flies. Further studies indicate that MitoCa2+ and Mitochondria–ER contacts (MERCs) form a positive feedback loop via IP3R to regulate autophagy independent of AMPK. Breakdown of this loop is responsible for MitoCa2+ reduction and ISC dysfunction in aged flies. Our results identify a regulatory module for autophagy initiation involving calcium crosstalk between the ER and mitochondria, providing a strategy to treat aging and age-related diseases.https://doi.org/10.1038/s41467-025-60196-4 |
| spellingShingle | Yao Zhang Peng Ma Saifei Wang Shuxin Chen Hansong Deng Restoring calcium crosstalk between ER and mitochondria promotes intestinal stem cell rejuvenation through autophagy in aged Drosophila Nature Communications |
| title | Restoring calcium crosstalk between ER and mitochondria promotes intestinal stem cell rejuvenation through autophagy in aged Drosophila |
| title_full | Restoring calcium crosstalk between ER and mitochondria promotes intestinal stem cell rejuvenation through autophagy in aged Drosophila |
| title_fullStr | Restoring calcium crosstalk between ER and mitochondria promotes intestinal stem cell rejuvenation through autophagy in aged Drosophila |
| title_full_unstemmed | Restoring calcium crosstalk between ER and mitochondria promotes intestinal stem cell rejuvenation through autophagy in aged Drosophila |
| title_short | Restoring calcium crosstalk between ER and mitochondria promotes intestinal stem cell rejuvenation through autophagy in aged Drosophila |
| title_sort | restoring calcium crosstalk between er and mitochondria promotes intestinal stem cell rejuvenation through autophagy in aged drosophila |
| url | https://doi.org/10.1038/s41467-025-60196-4 |
| work_keys_str_mv | AT yaozhang restoringcalciumcrosstalkbetweenerandmitochondriapromotesintestinalstemcellrejuvenationthroughautophagyinageddrosophila AT pengma restoringcalciumcrosstalkbetweenerandmitochondriapromotesintestinalstemcellrejuvenationthroughautophagyinageddrosophila AT saifeiwang restoringcalciumcrosstalkbetweenerandmitochondriapromotesintestinalstemcellrejuvenationthroughautophagyinageddrosophila AT shuxinchen restoringcalciumcrosstalkbetweenerandmitochondriapromotesintestinalstemcellrejuvenationthroughautophagyinageddrosophila AT hansongdeng restoringcalciumcrosstalkbetweenerandmitochondriapromotesintestinalstemcellrejuvenationthroughautophagyinageddrosophila |