Description:
Mitochondria play several roles in eukaryotes: they serve as main suppliers of energy; they are involved in apoptosis, in calcium homeostasis and in iron homeostasis. During the respiratory process, mitochondria produce reactive oxygen species (ROS), which can induce mutations in the mitochondrial DNA, leading to gradual deterioration of tissue function, that is reflected in the ageing process and in diseases associated with aging such as-diabetes, Parkinson and cancer. The present course will provide a panorama of the physiology of mitochondria, along with its different functions in the cell, emphasizing the contribution of damaged mitochondria to disease.
Aim:
The course intends to provide an up-to-date overview of the field
of mitochondrial research in health and disease.
Objectives:
1. Teach the students about the centrality of mitochondrial research in various fields
of research of biology.
2. Provide tools for understanding and appreciating studies in cellular biology in general and in mitochondrial research in particular.
3. Provide an overview of state of the art techniques in cellular biology.
4. Expose the students to cellular approaches in studying disease, as opposed to more common molecular approaches.
Structure:
The course consists of oral presentations.
Syllabus:
Syllabus:
1. Introduction: History of mitochondrial research. Evolution of mitochondria. Mitochondrial structure (inner, outer membrane, matrix, cristae). Overview of mitochondria's involvement in - energetics, ROS production, Ca++ homeostasis
2. The components of the respiratory chain: In the cell (respiration, mitochondrial potential, uncoupling)
3. Approaches to measure mitochondrial function: respirometry, mitochondrial probes for measuring potential and mitochondrial mass.
4. Reactive oxygen species: The mitochondria theory of ageing. How ROS are formed? The different types of ROS (superoxide, hydrogen peroxide…). How they are neutralized? (Superoxide dismutase, Catalase, Glutathione…). Their relevance to aging, disease and to physiology. Approaches to measure ROS.
5. Mitochondrial turnover I: Biogenesis (PGC1 alpha) and its regulation (AMPK, SIRT1)
6. Mitochondrial turnover II: mitochondrial clearance via autophagy (life cycle of mitochondria Parkin, Pink1, Nix)
6. Mitochondrial dynamics in Stem cells (Atan)
7. Mitochondria and thermogenesis: Brown adipose tissue, UCP1. Alternative pathways of proton leak. Synthetic uncouplers.
8. Mitochondria and calcium homeostasis. Import and export of mitochondrial calcium. The relative role of mitochondria in calcium homeostasis. (MCU, NCLX)
9. Mitochondrial proteins encoded by the nucleus: The transfer of genes from the mitochondria to the nucleus during evolution. The mechanism of import of mitochondrial proteins (Tim Tom). (guest lecturer: Abdussalam Azem)
10. Mitochondrial DNA: Characteristics of mitochondrial DNA, the genes encoded by mitochondrial DNA, heteroplasmy, TFAM
11. Mitochondria in apoptosis. The BCl2 family members. Cytochrome C release, mitochondrial transition pore. (Atan)
12. Mitochondria in disease I: Genetic diseases of mitochondria
13. Mitochondria in disease II: cancer metabolism in cancer
14. Mitochondria in disease III: Metabolic diseases obesity, diabetes
15. Summary and conclusions. Integration of mitochondrial membrane potential and respirometry into the analysis of a mitochondrial phenotype.