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Identifier |
000395148 |
Title |
Συντονισμός της μιτοχονδριακής βιογένεσης και του μηχανισμού της μιτοφαγίας κατά τη γήρανση στον νηματώδη Caenorhabditis elegans |
Alternative Title |
Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans |
Author
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Παληκαράς, Κωνσταντίνος
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Thesis advisor
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Ταβερναράκης, Νεκτάριος
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Reviewer
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Γαρίνης, Γιώργος
Σπηλιανάκης, Χαράλαμπος
Γραβάνης, Αχιλλέας
Μαυροθαλασσίτης, Γιώργος
Παπαματθαιάκης, Ιωσήφ
Χαλεπάκης, Γεώργιος
|
Abstract |
Mitochondria are ubiquitous membrane – bound organelles and they are a defining feature of
eukaryotic cell. The organelle is composed of a soluble matrix surrounded by a double
membrane, an ion impermeable inner membrane and a permeable outer membrane. Despite the fact that mitochondria contain their own independent genome, they are characterized as semiautonomous organelles because their biological functions rely on the expression of nuclear genes.
The mitochondrion is the site where electron transport chain and oxidative phosphorylation take place and provides the cell with the essential energy in the form of ATP for many cellular activities. Also, mitochondria are the major source of cellular reactive oxygen species (ROS) that cause oxidative damage to mtDNA, proteins and lipids. Accordingly, damaged, aged and excess mitochondria are a risk factor for the cell and proper elimination of them is important to maintain cellular homeostasis. Mitochondrial quality control mechanisms are therefore indispensable to cell survival and these include the removal of damaged mitochondrial proteins by an intra – organelle proteolytic system, the repair of damaged mitochondria by healthy ones through fission and fusion events and the removal of severely damaged mitochondria by autophagy (mitophagy).
Aberrant accumulation of mitochondria in disparate cell types is a shared hallmark of many
human pathologies and ageing. How mitochondrial biogenesis coordinates with the removal of damaged or superfluous mitochondria to maintain cellular homeostasis is not well understood.
Here, we show that mitophagy, a selective type of autophagy targeting mitochondria for
degradation, interfaces with mitochondrial biogenesis to regulate mitochondrial content in
Caenorhabditis elegans. We found that DCT-1 is a key mediator of mitophagy and longevity
assurance under conditions of stress in C. elegans. Impairment of mitophagy compromises stress resistance and triggers mitochondrial retrograde signalling through the SKN-1 transcription factor that regulates both mitochondrial biogenesis genes and mitophagy by enhancing DCT-1 expression. Our findings reveal a homeostatic feedback loop that integrates metabolic signals to coordinate the biogenesis and turnover of mitochondria. Uncoupling of these two processes during ageing contributes to overproliferation of damaged mitochondria and decline of cellular
function.
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Language |
Greek |
Subject |
Autophagy |
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Homeostasis |
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Mitochondria |
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Αυτοφαγία |
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Μιτοχόνδρια |
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Ομοιόσταση |
Issue date |
2015-07-14 |
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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Views |
472 |