Course Identification

Basic biochemistry

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:

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 (March 20^th)

2. The components of the respiratory chain: In the cell (respiration, mitochondrial potential, uncoupling) (March 27^th)

3. Approaches to measure mitochondrial function: respirometry, mitochondrial probes for measuring potential and mitochondrial mass.  (April 10^th)

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. (April 17^th)

5. Mitochondrial turnover: Biogenesis and mitochondrial clearance via autophagy (Parkin, Pink1, Nix, PGC-1alpha) (April 24^th)

6. Mitochondrial dynamics: the importance of shaping mitochondrial morphology (Atan) (May 1^st)

7.  Mitochondria and thermogenesis: Brown adipose tissue, UCP1. Alternative pathways of proton leak. Synthetic uncouplers. (May 8^th)

8. Mitochondria and calcium homeostasis. Import and export of mitochondrial calcium. The relative role of mitochondria in calcium homeostasis. (May 15^th)

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) (May 22^nd)

10. Mitochondrial DNA: Characteristics of mitochondrial DNA, the genes encoded by mitochondrial DNA, heteroplasmy, TFAM (May 29^th)

11. Mitochondria in apoptosis: The role of BCL-2 family members in regulating this process (Atan) (June 5^th)

12. Mitochondria in disease I: Metabolic diseases obesity, diabetes (June 12^th)

13. Mitochondria in disease II: Genetic diseases of mitochondria (June 19^th)

14. Mitochondria in disease III: cancer metabolism in cancer (June 26^th)

15. Summary and conclusions. Integration of mitochondrial membrane potential and respirometry into the analysis of a mitochondrial phenotype.   (July 4^th)

Upon successful completion of this course students should be able to:

1. Evaluate mitochondrial Oxphos function.

2. Analyze respirometry data.

3. Critically read articles related to mitochondrial research.

4. Assess the potential of mitochondrial involvement in disease.