HIF1a-dependent mitophagy facilitates cardiomyoblast differentiation
Mitophagy is thought to play a key role in eliminating damaged mitochondria, with diseases such as cancer and neurodegeneration exhibiting defects in this process. Mitophagy is also involved in cell differentiation and maturation, potentially through modulating mitochondrial metabolic reprogramming....
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Shared Science Publishers OG
2020-03-01
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| Series: | Cell Stress |
| Subjects: | |
| Online Access: | http://www.cell-stress.com/researcharticles/2020a-zhao-cell-stress/ |
| _version_ | 1818029301039104000 |
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| author | Jin-Feng Zhao Catherine E. Rodger George F. G. Allen Simone Weidlich Ian G. Ganley |
| author_facet | Jin-Feng Zhao Catherine E. Rodger George F. G. Allen Simone Weidlich Ian G. Ganley |
| author_sort | Jin-Feng Zhao |
| collection | DOAJ |
| description | Mitophagy is thought to play a key role in eliminating damaged mitochondria, with diseases such as cancer and neurodegeneration exhibiting defects in this process. Mitophagy is also involved in cell differentiation and maturation, potentially through modulating mitochondrial metabolic reprogramming. Here we examined mitophagy that is induced upon iron chelation and found that the transcriptional activity of HIF1a, in part through upregulation of BNIP3 and NIX, is an essential mediator of this pathway in SH-SY5Y cells. In contrast, HIF1a is dispensable for mitophagy occurring upon mitochondrial depolarisation. To examine the role of this pathway in a metabolic reprogramming and differentiation context, we utilised the H9c2 cell line model of cardiomyocyte maturation. During differentiation of these cardiomyoblasts, mitophagy increased and required HIF1a-dependent upregulation of NIX. Though HIF1a was essential for expression of key cardiomyocyte markers, mitophagy was not directly required. However, enhancing mitophagy through NIX overexpression, accelerated marker gene expression. Taken together, our findings provide a molecular link between mitophagy signalling and cardiomyocyte differentiation and suggest that although mitophagy may not be essential per se, it plays a critical role in maintaining mitochondrial integrity during this energy demanding process. |
| first_indexed | 2024-12-10T05:17:30Z |
| format | Article |
| id | doaj.art-1b8d21e6f9d545558d24530cf3ed4ed3 |
| institution | Directory Open Access Journal |
| issn | 2523-0204 |
| language | English |
| last_indexed | 2024-12-10T05:17:30Z |
| publishDate | 2020-03-01 |
| publisher | Shared Science Publishers OG |
| record_format | Article |
| series | Cell Stress |
| spelling | doaj.art-1b8d21e6f9d545558d24530cf3ed4ed32022-12-22T02:00:55ZengShared Science Publishers OGCell Stress2523-02042020-03-01459911310.15698/cst2020.05.220HIF1a-dependent mitophagy facilitates cardiomyoblast differentiationJin-Feng Zhao0Catherine E. Rodger1George F. G. Allen2Simone Weidlich3Ian G. Ganley4MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.Mitophagy is thought to play a key role in eliminating damaged mitochondria, with diseases such as cancer and neurodegeneration exhibiting defects in this process. Mitophagy is also involved in cell differentiation and maturation, potentially through modulating mitochondrial metabolic reprogramming. Here we examined mitophagy that is induced upon iron chelation and found that the transcriptional activity of HIF1a, in part through upregulation of BNIP3 and NIX, is an essential mediator of this pathway in SH-SY5Y cells. In contrast, HIF1a is dispensable for mitophagy occurring upon mitochondrial depolarisation. To examine the role of this pathway in a metabolic reprogramming and differentiation context, we utilised the H9c2 cell line model of cardiomyocyte maturation. During differentiation of these cardiomyoblasts, mitophagy increased and required HIF1a-dependent upregulation of NIX. Though HIF1a was essential for expression of key cardiomyocyte markers, mitophagy was not directly required. However, enhancing mitophagy through NIX overexpression, accelerated marker gene expression. Taken together, our findings provide a molecular link between mitophagy signalling and cardiomyocyte differentiation and suggest that although mitophagy may not be essential per se, it plays a critical role in maintaining mitochondrial integrity during this energy demanding process.http://www.cell-stress.com/researcharticles/2020a-zhao-cell-stress/mitophagyhif1anixbnip3iron chelationcardiomyocytedifferentiation |
| spellingShingle | Jin-Feng Zhao Catherine E. Rodger George F. G. Allen Simone Weidlich Ian G. Ganley HIF1a-dependent mitophagy facilitates cardiomyoblast differentiation Cell Stress mitophagy hif1a nix bnip3 iron chelation cardiomyocyte differentiation |
| title | HIF1a-dependent mitophagy facilitates cardiomyoblast differentiation |
| title_full | HIF1a-dependent mitophagy facilitates cardiomyoblast differentiation |
| title_fullStr | HIF1a-dependent mitophagy facilitates cardiomyoblast differentiation |
| title_full_unstemmed | HIF1a-dependent mitophagy facilitates cardiomyoblast differentiation |
| title_short | HIF1a-dependent mitophagy facilitates cardiomyoblast differentiation |
| title_sort | hif1a dependent mitophagy facilitates cardiomyoblast differentiation |
| topic | mitophagy hif1a nix bnip3 iron chelation cardiomyocyte differentiation |
| url | http://www.cell-stress.com/researcharticles/2020a-zhao-cell-stress/ |
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