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Content archived on 2024-05-29

Roadmap to Reactive Oxygen Species (ROS) homeostasis: analysis of ROS mediated signal transduction through PGC-1alpha coactivation and mitochondrial biogenesis

Objective

Mitochondrial dysfunction and oxidative stress are associated with neurodegenerative diseases, ischemia reperfusion injury of heart and brain, cancer and aging. Most research efforts regarding oxidative stress so far have focused on reactive oxygen species (ROS) mediated cell damage (oxidized lipids, protein and nucleic acids) and cell death (apoptosis and/or necrosis).

However, the role of hydrogen peroxide as a signalling molecule under physiological and pathophysiological conditions has been largely unexplored. In my recent study, we have identified a novel ROS homeostatic cycle dependent on the induction of PGC-1s. PGC-1alpha is a transcriptional coactivator that translates different physiological stimuli (cold, exercise, fasting) into specific metabolic programs (adaptive thermogenesis, muscle fiber-type switching, liver gluconeogenesis).

Indeed, PGC-1alpha has emerged as a master regulator of mitochondrial biogenesis and respiration. Hence, my future work will be based on this novel homeostatic cycle as a potential system to study ROS-mediated signalling pathways.

Future aims:
- to analyze and map the protein-signalling cascade: from hydrogen peroxide stimulation to induction of PGC-1alpha and ROS defence systems;
- to study the role of ROS as a more general transducer of environmental cues to PGC-1alpha induction and mitochondrial biogenesis;
- to study the role of PGC-1alpha, oxidative stress signalling, and mitochondrial biogenesis in malignant transformation models.

This research promises to increase the understanding of hydrogen peroxide as a signalling molecule, rather than its role as a general toxin. Furthermore, implementation of this novel ROS homeostatic system in models of diseases related to oxidative stress could aid tremendously in identifying new potential targets for therapeutic intervention.

Fields of science (EuroSciVoc)

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Keywords

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Topic(s)

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Call for proposal

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FP6-2004-MOBILITY-12
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Funding Scheme

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IRG - Marie Curie actions-International re-integration grants

Coordinator

TECHNION-ISRAEL INSTITUTE OF TECHNOLOGY
EU contribution
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Total cost

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