Doctoral theses
Current Record: 12 of 340
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Identifier |
000454533 |
Title |
Balanced mRNA storage and degradation regulates mitochondrial homeostasis, ageing and stress resistance in Caenorhabditis elegans. |
Alternative Title |
Η ισορροπημένη αποθήκευση και αποικοδόμηση των αγγελιοφόρων RNAs ρυθμίζει την ομοιόσταση των μιτοχονδρίων, τη γήρανση και την ανθεκτικότητα σε συνθήκες στρες στο νηματώδη Caenorhabditis elegans. |
Author
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Δασκαλάκη, Ιωάννα Α
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Thesis advisor
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Ταβερναράκης, Νεκτάριος
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Reviewer
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Δελιδάκης, Χρήστος
Γραβάνης, Αχιλλέας
Αλεξανδράκη, Δέσποινα
Γαρίνης, Γεώργιος
Παπατθαιάκης, Ιωσήφ
Σπηλιανάκης, Χαράλαμπος
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Abstract |
Mitochondrial abundance and function are essential regulators of healthspan and lifespan
in organisms as diverse as the nematode Caenorhabditis elegans and humans.
Importantly, their perturbation has been associated with various pathological conditions,
including lysosomal storage disease, cardiovascular disease, neurodegeneration and
type 2 diabetes mellitus, among others. Mitochondrial abundance is tightly regulated by
the two opposing processes of mitochondrial biogenesis and mitophagy. While mitophagy
has been extensively studied, mitochondrial biogenesis remains largely unexplored. This
is a complex, multi-step process coordinated by retrograde and anterograde responses.
Local translation of nuclear-encoded and mitochondrial-targeted transcripts (NEMTTs) in
the vicinity of mitochondria is crucial for the organelle biogenesis. Although cytoplasmic
factors are expected to principally regulate local translation under normal conditions and
in response to stress, the identity of such factors remain elusive. Here, we uncover a
pivotal role for cytoplasmic components known to participate in the 5’-3’ mRNA
degradation pathway, in regulating mitochondrial abundance and function in C. elegans.
Specifically, we show that the mRNA decapping and the CCR-4/NOT complexes form
distinct foci that physically associate with mitochondria and oppositely regulate
mitochondrial abundance during ageing. The underlying mechanism relies on the posttranscriptional regulation of NEMTTs in the vicinity of the organelle. Balanced mRNA
degradation and storage of target NEMTTs is required for the regulation of mitochondrial
abundance and function, ultimately promoting stress resistance and longevity in C.
elegans. Our findings uncover a novel role for mRNA metabolism components in
mitochondrial biogenesis and identify the cytoplasmic constituents that fine-tune local
translation during ageing and under conditions of stress in C. elegans.
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Language |
English |
Subject |
Mitochondria |
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Nematode C. Elegans |
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mRNA degradation |
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mRNA storage |
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Αποθήκευση mRNA |
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Αποικοδόμηση mRNA |
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Μιτοχόνδρια |
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Νηματώδης C. Elegans |
Issue date |
2023-05-26 |
Collection
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School/Department--School of Sciences and Engineering--Department of Biology--Doctoral theses
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Type of Work--Doctoral theses
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Permanent Link |
https://elocus.lib.uoc.gr//dlib/0/e/7/metadata-dlib-1679911890-967628-11886.tkl
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Views |
801 |