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Mitochondrial maturation drives germline stem cell differentiation in Caenorhabditiselegans

The C. elegans germline recapitulates mammalian stem cell niches and provides an effective platform for investigating key aspects of stem cell biology. However, the molecular and physiological requirements for germline stem cell homeostasis remain largely elusive. Here, we report that mitochondrial...

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Autores principales: Charmpilas, Nikolaos, Tavernarakis, Nektarios
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206027/
https://www.ncbi.nlm.nih.gov/pubmed/31217501
http://dx.doi.org/10.1038/s41418-019-0375-9
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author Charmpilas, Nikolaos
Tavernarakis, Nektarios
author_facet Charmpilas, Nikolaos
Tavernarakis, Nektarios
author_sort Charmpilas, Nikolaos
collection PubMed
description The C. elegans germline recapitulates mammalian stem cell niches and provides an effective platform for investigating key aspects of stem cell biology. However, the molecular and physiological requirements for germline stem cell homeostasis remain largely elusive. Here, we report that mitochondrial biogenesis and function are crucial for germline stem cell identity. We show that general transcription activity in germline mitochondria is highly compartmentalized, and determines mitochondrial maturation. RPOM-1, the mitochondrial RNA polymerase, is differentially expressed as germ nuclei progress from the distal to the proximal gonad arm to form oocytes. Mitochondria undergo changes from globular to tubular morphology and become polarized, as they approach the proximal gonad arm. Notably, this mitochondrial maturation trajectory is evolutionarily conserved. We find that a similar transition and temporal mitochondrial RNA polymerase expression profile characterizes differentiation of mammalian stem cells. In C. elegans, ATP, and ROS production increases sharply during maturation. Impaired mitochondrial bioenergetics causes gonad syncytium tumor formation by disrupting the balance between mitosis and differentiation to oocytes, which results in a marked reduction of fecundity. Consequently, compensatory apoptosis is induced in the germline. Sperm-derived signals promote mitochondrial maturation and proper germ cell differentiation via the MEK/ERK kinase pathway. Germ cell fate decisions are determined by a crosstalk between Insulin/IGF-1 and TGF-β signaling, mitochondria and protein synthesis. Our findings demonstrate that mitochondrial transcription activity determines a shift in mitochondrial bioenergetics, which in turn regulates germline stem cell survival and differentiation. Perturbation of mitochondrial transcription hinders proper germ cell differentiation and causes germline tumor development.
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spelling pubmed-72060272020-05-08 Mitochondrial maturation drives germline stem cell differentiation in Caenorhabditiselegans Charmpilas, Nikolaos Tavernarakis, Nektarios Cell Death Differ Article The C. elegans germline recapitulates mammalian stem cell niches and provides an effective platform for investigating key aspects of stem cell biology. However, the molecular and physiological requirements for germline stem cell homeostasis remain largely elusive. Here, we report that mitochondrial biogenesis and function are crucial for germline stem cell identity. We show that general transcription activity in germline mitochondria is highly compartmentalized, and determines mitochondrial maturation. RPOM-1, the mitochondrial RNA polymerase, is differentially expressed as germ nuclei progress from the distal to the proximal gonad arm to form oocytes. Mitochondria undergo changes from globular to tubular morphology and become polarized, as they approach the proximal gonad arm. Notably, this mitochondrial maturation trajectory is evolutionarily conserved. We find that a similar transition and temporal mitochondrial RNA polymerase expression profile characterizes differentiation of mammalian stem cells. In C. elegans, ATP, and ROS production increases sharply during maturation. Impaired mitochondrial bioenergetics causes gonad syncytium tumor formation by disrupting the balance between mitosis and differentiation to oocytes, which results in a marked reduction of fecundity. Consequently, compensatory apoptosis is induced in the germline. Sperm-derived signals promote mitochondrial maturation and proper germ cell differentiation via the MEK/ERK kinase pathway. Germ cell fate decisions are determined by a crosstalk between Insulin/IGF-1 and TGF-β signaling, mitochondria and protein synthesis. Our findings demonstrate that mitochondrial transcription activity determines a shift in mitochondrial bioenergetics, which in turn regulates germline stem cell survival and differentiation. Perturbation of mitochondrial transcription hinders proper germ cell differentiation and causes germline tumor development. Nature Publishing Group UK 2019-06-19 2020-02 /pmc/articles/PMC7206027/ /pubmed/31217501 http://dx.doi.org/10.1038/s41418-019-0375-9 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Charmpilas, Nikolaos
Tavernarakis, Nektarios
Mitochondrial maturation drives germline stem cell differentiation in Caenorhabditiselegans
title Mitochondrial maturation drives germline stem cell differentiation in Caenorhabditiselegans
title_full Mitochondrial maturation drives germline stem cell differentiation in Caenorhabditiselegans
title_fullStr Mitochondrial maturation drives germline stem cell differentiation in Caenorhabditiselegans
title_full_unstemmed Mitochondrial maturation drives germline stem cell differentiation in Caenorhabditiselegans
title_short Mitochondrial maturation drives germline stem cell differentiation in Caenorhabditiselegans
title_sort mitochondrial maturation drives germline stem cell differentiation in caenorhabditiselegans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206027/
https://www.ncbi.nlm.nih.gov/pubmed/31217501
http://dx.doi.org/10.1038/s41418-019-0375-9
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