Mitochondria research areas

MIT 20.109 Spring 2008 Research Proposal

Red WF Team (Evan Hefner and Stephanie Yaung)

Areas of interest regarding mitochondria research and regenerative medicine

• Mitochondria "cell" cultures -- Self-sustaining mitochondria may require cytoskeletal-like scaffolds and modified plasmids with necessary proteins encoded by nuclear and not mitochondrial DNA; uses for these cultures?
• Mitochondrial diseases -- use genetic engineering to treat accelerated aging that arises from deletions accumulated in mitochondrial DNA; targeted gene therapy?
• Nuclearize mitochondrial DNA

Current methods and publications:

• Mitochondria isolation

http://www.piercenet.com/Products/Browse.cfm?fldID=45F252F7-2410-40C9-81CD-57B19AA095DB

• Vermulst M, Wanagat J, Kujoth GC, Bielas JH, Rabinovitch PS, Prolla TA, Loeb LA. (2008) DNA deletions and clonal mutations drive premature aging in mitochondrial mutator mice. Nature Genetics 40 , 392-394.

Mutant polymerase gamma (PolgA) that contains a proofreading-deficient subunit causes an increase in mitochondrial DNA (mtDNA) mutations by hindering homology-directed DNA repair mechanisms. mtDNA mutations play a role in aging that may vary among different tissues, where deletions accumulate the most in the brain and heart. With defective PolgA, there are more mtDNA mutations, the deletions accumulate at an accelerated rate, and the mice have a shortened lifespan.

• Mitochondria: more than just a powerhouse. http://www.ncbi.nlm.nih.gov/pubmed/16860735
• Characterization of the human heart mitochondrial proteome. http://www.ncbi.nlm.nih.gov/pubmed/12592411
• Vimentin supports mitochondrial morphology and organization. http://www.ncbi.nlm.nih.gov/pubmed/17983357
• Protein transport into mitochondria. http://www.ncbi.nlm.nih.gov/pubmed/10744987