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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

Παληκαράς, Κωνσταντίνος

Thesis advisor

Ταβερναράκης, Νεκτάριος

Reviewer

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.

Language

Greek

Subject

Autophagy

Homeostasis

Mitochondria

Αυτοφαγία

Μιτοχόνδρια

Ομοιόσταση

Issue date

2015-07-14

Collection