Readings

Course readings.
WEEK #	TOPICS	READINGS
1	Introduction of instructor and students and course overview See the Lecture Summary	[No Readings]
2	The vulnerability of mtDNA and consequences of oxidative damage See the Lecture Summary	Paper 1 Richter, C., J. W. Park, and B. Ames. "Normal Oxidative Damage to Mitochondrial DNA is Extensive." PNAS 85 (1988): 6465-67. (PDF) Paper 2 Pinz, K. G., S. Shibutani, and D. F. Bogenhagen. "Action of Mitochondrial DNA Polymerase γ at Sites of Base Loss or Oxidative Damage." The Journal of Biological Chemistry 270 (1988): 9202-06.
3	Repair of 8-oxoG from the mitochondrial genome: The importance of OGG1 and base excision repair pathways See the Lecture Summary	Paper 1 Dobson, A. W., Y. Xu, M. R. Kelley, S. P. LeDoux, and G. Wilson. "Enhanced Mitochondrial DNA Repair and Cellular Survival after Oxidative Stress by Targeting the Human 8-Oxoguanine Glycosylase Repair Enzyme to the Mitochondria." Journal of Biological Chemistry 275 (2000): 37518-23. Paper 2 De Souza-Pinto, N. C., L. Eide, B. Hogue, T. Thybo, T. Stevsner, E. Seeberg, A. Klungland, and V. Bohr. "Repair of 8-Oxodeoxyguanosine Lesions in the Mitochondrial DNA Depends on the Oxoguanine DNA Glycosylase (OGG1) Gene and 8-Oxoguanine Accumulates in the Mitochondrial DNA of OGG1-defective Mice." Cancer Research 61 (2001): 5378-81.
4	The mitochondrial theory of aging and the importance of OGG1 See the Lecture Summary	Paper 1 Stuart, J. A., B. M. Bourque, N. C. de Souza-Pinto, and V. A. Bohr. "No Evidence of Mitochondrial Respiratory Dysfunction in OGG1-null Mice Deficient in Removal of 8-oxodeoxyguanine from the Mitochondrial DNA." Free Radical Biology & Medicine 38 (2005): 737-45. Paper 2 Bacsi, A., G. Chodaczek, T. K. Hazra, D. Konkel, and I. Boldogh. "Increased ROS Generation in Subsets of OGG1 Knockout Fibroblast Cells." Mechanisms of Ageing and Development 128 (2007): 637-49.
5	Mouse models for mtDNA mutation and aging See the Lecture Summary	Paper 1 Kujoth G. C., A. Hiona, T. D. Pugh, S. Someya, K. Panzer, S. E. Wohlgemuth, T. Hofer, A. Y. Seo, R. Sullivan, W. A. Jobling, J. D. Morrow, H. Van Remmen, J. M. Sedivy, T. Yamasoba, M. Tanokura, R. Weindruch, C. Leeuwenburgh, and T. A. Prolla. "Mitochondrial DNA Mutations, Oxidative Stress, and Apoptosis in Mammalian Aging." Science 309 (2005): 481-4. Paper 2 Vermulst M., J. H. Bielas, G. C. Kujoth, W. C. Ladiges, P. S. Rabinovitch, T. A. Prolla, and L. A. Loeb. "Mitochondrial Point Mutations Do Not Limit the Natural Lifespan of Mice." Nature Genetics 39 (2007): 540-43.
6	Oxidative damage and base excision repair in Alzheimer's disease See the Lecture Summary	Paper 1 Wang J., S. Xiong, C. Xie, W. R. Markesberry, and M. A. Lovell. "Increased Oxidative Damage in Nuclear and Mitochondrial DNA in Alzheimer's Disease." Journal of Neuorchemistry 93 (2005): 953-62. Paper 2 Weissman L., J. Dong-Gyu, M. M. Sorensn, N. C. de Souza-Pinto, W. R. Merkesberry, M. P. Mattson, and V. A. Bohr. "Defective DNA Base Excision Repair in Brain from Individuals with Alzheimer's Disease and Amnestic Mild Cognitive Impairment." Nucleic Acids Research 35 (2007): 5545-55. (PDF)
7	mtDNA deletions in neurons and the importance of oxidative phosphorylations See the Lecture Summary	Paper 1 Kratsberg Y., E. Kudryavtseva, A. McKee, C. Geula, N. Kowall, and K. Khrapko. "Mitochondrial DNA Deletions are Abundant and Cause Functional Impairment in Aged Human Substantia Nigra Neurons." Nature Genetics 38 (2006): 518-20. Paper 2 Sung H. J., W. Ma, P. Y. Wang, J. Hynes, T. C. O'Riordan, C. A. Combs, J. P. McCoy Jr., F. Bunz, J. G. Kang, and P. M. Hwang. "Mitochondrial Respiration Protects Against Oxygen-Associated DNA Damage." Nature Communications 1 (2010): 1-8.
8	Quality control of mtDNA: The bottleneck and mitochondrial fusion See the Lecture Summary	Paper 1 Ono T., K. Isobe, K. Nakada, and J. Hayashi. "Human Cells are Protected from Mitochondrial Dysfunction by Complementation of DNA Products in Fused Mitochondria." Nature Genetics 28 (2001) 272-5. Paper 2 Fan W., K. G. Waymire, N. Narula, P. Li, C. Rocher, P. E. Coskun, M. A. Vannan, J. Narula, G. R. Macgregor, and D. C. Wallace. "A Mouse Model of Mitochondrial Disease Reveals Germline Selection Against Severe mtDNA Mutations." Science 319 (2008): 958-62.
9	From yeast to humans: Conservation of Polγ See the Lecture Summary	Paper 1 Graziewicz M., R. Bienstock, and W. Copeland. "The DNA Polymerase γ Y955C Disease Variant Associated with PEO and Parkinsonism Mediates the Incorporation and Translesion Synthesis Opposite 7,8-dihydro-8-oxo-2'-deoxyguanosine." Human Molecular Genetics 16 (2007): 2729-39. Paper 2 Stumpf J., C. M. Bailey, D. Spell, M. Stillwagon, K. Anderson, and W. Copeland. "mip1 Containing Mutations Associated with Mitochondrial Disease Causes Mutagenesis and Depletion of mtDNA in Saccharomyces Cerevisiae." Human Molecular Genetics 19 (2010): 2123-33.
10	Determination of nuclear encoded genes that contribute to mitochondrial disorders See the Lecture Summary	Paper 1 Spinazzola A., C. Viscomi, E. Fernandez-Vizarra, F. Carrara, P. D'Adamo, S. Calvo, R. M. Marsano, C. Donnini, H. Weiher, P. Strisciuglio, R. Parini, E. Sarzi, A. Chan, S. DiMauro, A. Rötig, P. Gasparini, I. Ferrero, V. K. Mootha, V. Tiranti, and M. Zeviani. "MPV17 Encodes an Inner Mitochondrial Membrane Protein and is Mutated in Infantile Hepatic Mitochondrial DNA Depletion." Nature Genetics 38 (2006): 570-75. Paper 2 Sugiana C., D. J. Pagliarini, M. McKenzie, D. M. Kirby, R. Salemi, K. K. Abu-Amero, H. H. Dahl, W. M. Hutchison, K. A. Vascotto, S. M. Smith, R. F. Newbold, J. Christodoulou, S. Calvo, V. K. Mootha, M. T. Ryan, and D. R. Thorburn. "Mutations of C20orf7 Disrupts Complex I Assembly and Causes Lethal Neonatal Mitochondrial Disease." American Journal of Human Genetics 83 (2008): 468-78.
11	Field trip to the Laboratory of Vamsi Mootha at Massachusetts General Hospital See the Lecture Summary	[No Readings]
12	mtDNA in cancer and chemotherapeutic resistance See the Lecture Summary	Paper 1 Carew J. S., Y. Zhou, M. Albitar, J. D. Carew, M. J. Keating, and P. Huang. "Mitochondrial DNA Mutations in Primary Leukemia Cells After Chemotherapy: Clinical Significance and Therapeutic Implications." Leukemia 17 (2003): 1437-47. Paper 2 Mizutani S., Y. Miyato, Y. Shidara, S. Asoh, A. Tokunaga, T. Tajiri, and S. Ohta. "Mutations in the Mitochondrial Genome Confer Resistance of Cancer Cells to Anticancer Drugs." Cancer Science 100 (2009): 1680-87.
13	Levels of ROS in the mitochondria of cancer cells See the Lecture Summary	Paper 1 Park J. S., L. K. Sharma, H. Li, R. Xiang, D. Holstein, J. Wu, J. Lechleiter, S. L. Naylor, J. J. Deng, J. Lu, and Y. Bai. "A Heteroplasmic, not Homoplasmic, Mitochondrial DNA Mutation Promotes Tumorigenesis via Alteration in Reactive Oxygen Species Generation and Apoptosis." Human Molecular Genetics 18 (2009): 1578-89. Paper 2 Kulawiec M., K. M. Owens, and K. Singh. "Cancer Cell Mitochondria Confer Apoptosis Resistance and Promote Metastasis." Cancer Biology and Therapy 8 (2009): 1378-85.
14	Oral presentations See the Lecture Summary	[No Readings]