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Mitochondrial remodelling is essential for female germ cell differentiation and survival.
In: PLoS Genetics, Jg. 18 (2023-01-25), Heft 1, S. 1-31
Online
academicJournal
Zugriff:
Stem cells often possess immature mitochondria with few inner membrane invaginations, which increase as stem cells differentiate. Despite this being a conserved feature across many stem cell types in numerous organisms, how and why mitochondria undergo such remodelling during stem cell differentiation has remained unclear. Here, using Drosophila germline stem cells (GSCs), we show that Complex V drives mitochondrial remodelling during the early stages of GSC differentiation, prior to terminal differentiation. This endows germline mitochondria with the capacity to generate large amounts of ATP required for later egg growth and development. Interestingly, impairing mitochondrial remodelling prior to terminal differentiation results in endoplasmic reticulum (ER) lipid bilayer stress, Protein kinase R-like ER kinase (PERK)-mediated activation of the Integrated Stress Response (ISR) and germ cell death. Taken together, our data suggest that mitochondrial remodelling is an essential and tightly integrated aspect of stem cell differentiation. This work sheds light on the potential impact of mitochondrial dysfunction on stem and germ cell function, highlighting ER lipid bilayer stress as a potential major driver of phenotypes caused by mitochondrial dysfunction. Author summary: Stem cells are necessary for both tissue development and regeneration. As stem cells differentiate into specialized cells their mitochondria often undergo changes, including the remodelling of their inner mitochondrial membranes. Using a population of adult germline stem cells in the Drosophila ovary, we show that mitochondrial remodelling during differentiation acts to endow germline mitochondria with the capacity to generate large amounts of ATP, which are required for later egg growth and development. Interestingly, we also find that impairing mitochondrial remodelling induces endoplasmic reticulum stress, which results in premature termination of differentiation and eventual cell death. Our work illuminates the potential impact of mitochondrial dysfunction on stem cell function and differentiation, and potential mechanisms of mitochondrial disease. [ABSTRACT FROM AUTHOR]
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Mitochondrial remodelling is essential for female germ cell differentiation and survival.
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Autor/in / Beteiligte Person: | Monteiro, Vernon Leander ; Safavian, Darya ; Vasudevan, Deepika ; Hurd, Thomas Ryan |
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Zeitschrift: | PLoS Genetics, Jg. 18 (2023-01-25), Heft 1, S. 1-31 |
Veröffentlichung: | 2023 |
Medientyp: | academicJournal |
ISSN: | 1553-7390 (print) |
DOI: | 10.1371/journal.pgen.1010610 |
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