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Identifier 000424571
Title A mitochondrial rheostat drives germline stem cell differentiation in Caenorhabditis elegans
Alternative Title Ένας μιτοχονδριακός ροοστάτης καθοδηγεί την διαφοροποίηση των γαμετικών βλαστικών κυττάρων στον Caenorhabditis elegans
Author Χαρμπίλας, Νικόλαος
Thesis advisor Ταβερναράκης, Νεκτάριος
Reviewer Αλεξανδράκη, Δέσποινα
Μαυροθαλασσίτης, Γεώργιος
Δελιδάκης, Χρήστος
Καλαντίδης, Κρίτων
Βόντας, Ιωάννης
Νικολετοπούλου, Βασιλική
Abstract The C. elegans germline recapitulates mammalian stem cell niches, and has proven instrumental in understanding key aspects of stem cell biology. However, the molecular and physiological requirements for germline stem cell homeostasis remain largely elusive. We investigated the role of mitochondrial biogenesis and function in the preservation of germline stem cell identity. Here, we show that general transcription activity in germline mitochondria is highly compartmentalized and parallels mitochondrial maturation. Expression of RPOM-1, the mitochondrial RNA polymerase, increases as germ nuclei progress from the distal to the proximal gonadal arm to form oocytes, and is directly regulated by IFET-1, a translational repressor required for normal P granule formation. Mitochondria transition from globular to tubular morphology and become polarized, as they approach the proximal gonad arm. Notably, we find that a similar transition and temporal mitochondrial RNA polymerase expression profile characterizes differentiation of mammalian stem cells. This shift is accompanied by increased ATP and ROS production. Perturbation of mitochondrial bioenergetics causes gonad syncytium hyperplasia by disrupting the balance between mitosis and differentiation to oocytes, resulting in a marked reduction of fecundity. Consequently, compensatory apoptosis is induced in the germline. Sperm-derived signals promote mitochondrial maturation and 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 a shift in mitochondrial bioenergetics guides germline stem cell differentiation, and implicate mitochondrial transcription in germ cell differentiation and germline tumor development.
Language English
Subject Apoptosis
Γαμετική σειρά
Issue date 2019-11-29
Collection   Faculty/Department--Faculty of Sciences and Engineering--Department of Biology--Doctoral theses
  Type of Work--Doctoral theses
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