Our primary research focus is on the regulation of mitochondrial chromatin, and its effect on genome segregation, compaction, and expression. By analogy to the nuclear genome, whose regulated compaction/decompaction is an essential aspect of replication, transcription and transmission, regulated compaction of the mitochondrial genome is likely to be a key aspect of mitochondrial biology. The core of our research lies in determining how the mitochondrial genome is maintained and regulated, and how that regulation affects developmental and physiological aspects of mitochondrial function in health and disease. This work has implications in diabetes, aging, heart disease, and mtDNA-borne birth defects.
We have several thrusts in the lab as of now: 1) mutations affecting mtDNA compaction in cardiovascular disease, 2) post-translational regulation of mtDNA compaction, 3) environmental causes of mtDNA depletion and 3) identification and characterization of protein-mtDNA complexes.
Kaufman, Brett A. Durisic, Nela. Mativetsky, Jeffrey M. Costantino, Santiago. Hancock, Mark A. Grutter, Peter. Shoubridge, Eric A. The mitochondrial transcription factor TFAM coordinates the assembly of multiple DNA molecules into nucleoid-like structures. Molecular Biology of the Cell 18: 3225-36, 2007.Leary, Scot C. Cobine, Paul A. Kaufman, Brett A. Guercin, Guy-Hellen. Mattman, Andre. Palaty, Jan. Lockitch, Gillian. Winge, Dennis R. Rustin, Pierre. Horvath, Rita. Shoubridge, Eric A. The human cytochrome c oxidase assembly factors SCO1 and SCO2 have regulatory roles in the maintenance of cellular copper homeostasis.[erratum appears in Cell Metab. 2007 May;5(5):403]. Cell Metabolism 5: 9-20, 2007.Chen, Xin Jie. Wang, Xiaowen. Kaufman, Brett A. Butow, Ronald A. Aconitase couples metabolic regulation to mitochondrial DNA maintenance. Science 307: 714-7, 2005.Leary, Scot C. Kaufman, Brett A. Pellecchia, Giovanna. Guercin, Guy-Hellen. Mattman, Andre. Jaksch, Michaela. Shoubridge, Eric A. Human SCO1 and SCO2 have independent, cooperative functions in copper delivery to cytochrome c oxidase. Human Molecular Genetics 13: 1839-48, 2004.Kaufman, Brett A. Kolesar, Jill E. Perlman, Philip S. Butow, Ronald A. A function for the mitochondrial chaperonin Hsp60 in the structure and transmission of mitochondrial DNA nucleoids in Saccharomyces cerevisiae. Journal of Cell Biology 163: 457-61, 2003.Kaufman, Brett A. Newman, Scott M. Perlman, Philip S. Butow, Ronald A. Crosslinking of proteins to mtDNA. Methods in Molecular Biology 197: 377-89, 2002.Kaufman, B A. Newman, S M. Hallberg, R L. Slaughter, C A. Perlman, P S. Butow, R A. In organello formaldehyde crosslinking of proteins to mtDNA: identification of bifunctional proteins. Proceedings of the National Academy of Sciences of the United States of America 97: 7772-7, 2000.Weraarpachai W, Antonicka H, Sasarman F, Seeger J, Schrank B, Kolesar JE, Lochmüller H, Chevrette M, Kaufman BA, Horvath R, Shoubridge EA. Mutation in TACO1, encoding a translational activator of COX I, results in cytochrome c oxidase deficiency and late-onset Leigh syndrome Nature Genetics 41: 833-7, 2009.Campbell, Christopher T. Kolesar, Jill E. Kaufman Brett A. Mitochondrial transcription factor A regulates mitochondrial transcription initiation, DNA packaging, and genome copy number. Biochimica et biophysica acta 1819: 921-9, 2012.Mallilankaraman Karthik, Cárdenas César, Doonan Patrick J, Chandramoorthy Harish C, Irrinki Krishna M, Golenár Tünde, Csordás György, Madireddi Priyanka, Yang Jun, Müller Marioly, Miller Russell, Kolesar Jill E, Molgó Jordi, Kaufman Brett, Hajnóczky György, Foskett J Kevin, Madesh Muniswamy MCUR1 is an essential component of mitochondrial Ca(2+) uptake that regulates cellular metabolism. Nature cell biology : , 2012.Kolesar Jill E, Wang Catherine Y, Taguchi Yumiko V, Chou Shih-Hsuan, Kaufman Brett A Two-dimensional intact mitochondrial DNA agarose electrophoresis reveals the structural complexity of the mammalian mitochondrial genome. Nucleic acids research : , 2012.Soubannier Vincent, Rippstein Peter, Kaufman Brett A, Shoubridge Eric A, McBride Heidi M Reconstitution of mitochondria derived vesicle formation demonstrates selective enrichment of oxidized cargo. PloS one 7: e52830, 2012.