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Identifier

000451470

Title

Regulation and roles of mitochondrial metabolism in ageing and stress

Alternative Title

Ο ρόλος και η ρύθμιση του μιτοχονδριακού μεταβολισμού στη γήρανση και απόκριση σε στρες

Author

Γκίκας, Ηλίας Χ

Thesis advisor

Ταβερναράκης, Νεκτάριος

Reviewer

Δελιδάκης, Χρήστος
Γαρίνης, Γιώργος
Αλεξανδράκη, Δέσποινα
Ταλιανίδης, Γιάννης
Σπηλιανάκης, Χαράλαμπος
Παυλόπουλος, Αναστάσιος

Abstract

Mitochondria are intracellular organelles fine-tuning a plethora of energy releasing and consuming processes essential for cell life and death. Mitochondrial dysfunction abbreviates premature ageing and various metabolic disorders including, but not limited to, cancer and neurodegeneration. To maintain mitochondrial homeostasis, sophisticated molecular responses balancing mitochondrial clearance and biogenesis have emerged. The aim of the first part of this study was to investigate the role of mitochondrial protein import system in ageing, using Caenorhabditis elegans as a model organism. We found that mitochondrial protein import system regulates mitochondria number and function. Specifically, we showed that reduced mitochondrial content elicits a distinct longevity paradigm. Importantly, we reported that metabolic rewiring towards glycolysis and de novo serine biosynthesis is causatively linked to longevity. The aim of the second part of this study was to explore the role of mitochondria in organismal survival upon hypoxia. On a cellular level, reduction of mitochondrial respiration and increased glycolysis as an alternative energy source, are commonly observed in hypoxic cells. These alterations are mainly attributed to the activity of hypoxia-inducible factor 1 (HIF-1). Interestingly, we reported that mitochondrial respiration is more prevalent than or act in parallel to glycolysis in response to hypoxia. Interestingly, we found that proteins involved in mitochondrial phospholipid trafficking namely, MDMH-35 and its interacting partners B0334.4 (PRELID-1) and F15D3.6 (PRELID-3), cooperate to preserve mitochondrial function both in the presence and absence of oxygen. We suggest that balanced mitochondrial phospholipid content is necessary for survival under hypoxia, independently of HIF-1. Overall, the findings provided in this thesis highlight the regulation and roles of mitochondrial metabolism in ageing and stress.

Language

English

Subject

Hypoxia

Mitochondria

Phospholipid metabolism

Protein import system

Serine biosynthesis

Βιοσύνθεση σερίνης

Μεταβολισμός φωσφολιπιδίων

Μηχανισμός εισόδου πρωτεϊνών στα μιτοχόνδρια

Μιτοχόνδρια