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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 Δασκαλάκη, Ιωάννα Α
Thesis advisor Ταβερναράκης, Νεκτάριος
Reviewer Δελιδάκης, Χρήστος
Γραβάνης, Αχιλλέας
Αλεξανδράκη, Δέσποινα
Γαρίνης, Γεώργιος
Παπατθαιάκης, Ιωσήφ
Σπηλιανάκης, Χαράλαμπος
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.
Language English
Subject Mitochondria
Nematode C. Elegans
mRNA degradation
mRNA storage
Αποθήκευση mRNA
Αποικοδόμηση mRNA
Μιτοχόνδρια
Νηματώδης C. Elegans
Issue date 2023-05-26
Collection   School/Department--School of Sciences and Engineering--Department of Biology--Doctoral theses
  Type of Work--Doctoral theses
Permanent Link https://elocus.lib.uoc.gr//dlib/0/e/7/metadata-dlib-1679911890-967628-11886.tkl Bookmark and Share
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