Powerhouse rules: the role of mitochondria in human diseases

Lectures: 1 session / week, 2 hours / session

7.03 Genetics

7.05 General Biochemistry

7.06 Cell Biology

7.08 Biological Chemistry II

The primary role of mitochondria is to produce 90% of a cell's energy in the form of ATP through a process called oxidative phosphorylation. Oxidative phosphorylation is carried out in a chain of five protein complexes located in the mitochondrial membrane. The mammalian mitochondrial genome, which is a double-stranded circular molecule about 16,500 nucleotides in length, encodes 37 genes. Of these genes, 13 encode polypeptides that are part of the oxidative phosphorylation machinery, while the remaining genes encode protein synthesis machinery that operates in the mitochondria. Importantly, a byproduct of oxidative phosphorylation is the production of Reactive Oxygen Species (ROS), which are chemically reactive molecules that are capable of damaging many cellular components, including DNA. A low level of ROS production is normal, and cells are equipped with antioxidant defenses that can disarm low levels of ROS.

A variety of clinical disorders have been shown to include "mitochondrial dysfunction," which loosely refers to defective oxidative phosphorylation and usually coincides with the occurrence of excess ROS production, placing cells under oxidative stress. A known cause and effect of oxidative stress is damage to and mutation of mitochondrial DNA. We will use this class to explore issues relating to mitochondrial DNA integrity and how it can be damaged, repaired, mutated, and compromised in human diseases.

At the end of this class, students should be able to:

This seminar will meet weekly for 2 hours. For each class, students will be required to have read two research papers assigned by the instructor. Prior to each class, students should prepare two questions about each assigned paper. The questions may be about the background, the results, the conclusions, or the methods used. During class there will be a group discussion of the assigned papers.

This course will be graded Pass/Fail. Grading will be based on reading the assigned papers and preparing the questions, participating in the class discussions, and satisfactorily fulfilling the oral and written assignments.

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