Department of Biochemistry & Molecular Biology
Carolyn Suzuki, B.Sc., Ph.D.
Dr. Suzuki received her Ph.D. (1992) from the Johns Hopkins University conducting her thesis research with Richard
D. Klausner, M.D. at the National Institutes of Health, USA. She was a post-doctoral fellow with Gottfried Schatz,
Ph.D. at the Biozentrum in Basel, Switzerland. Dr. Suzuki received a Damon Runyon Cancer Research Foundation
fellowship and a Basil O'Connor Scholars Award. Her research focuses on the function of ATP-dependent proteases
and chaperones in mitochondrial homeostasis, cell signaling and apoptosis.
B.Sc., 1984, University of Illinois at Urbana, Biological Sciences
Ph.D., 1992, Johns Hopkins University, Cell Biology
|Strauss, K.A., Jinks, R.N., Puffenberger, E.G. Venkatesh, S., Singh, K., Cheng, I., Mikita, N., Thilagavathi, J., Lee, J., Sarafianos, S., Benkert, A., Koehler, A., Zhu, A., Trovillion.V., McGlincy, M., Morlet, T., Deardorff, M., Innes, A.M., Prasad, C., Chudley, A.E., Lee, I.N.W., and Suzuki, C.K. CODAS syndrome is associated with mutations of LONP1 encoding mitochondrial AAA+ Lon protease. Am. J. Hum. Genet. . 96, 121–135 (2015).|
|Lu B, Lee J, Nie X, Li M, Morozov YI, Venkatesh S, Bogenhagen DF, Temiakov D, Suzuki CK. Phosphorylation of human TFAM in mitochondria impairs DNA binding and promotes degradation by the AAA+ Lon protease. Molecular Cell, 49:121 (2013). (2013).|
|Bernstein, S.H., Venkatesh, S. Li, M., Lee, J., Lu B., Hilchey, S.P., Morse, K.M., Metcalf, H.M., Andreeff, M., Brookes, P.S. and Suzuki, C.K., The mitochondrial ATP-dependent Lon protease: a novel drug target in lymphoma death mediated by the synthetic triterpenoids CDDO and its derivatives. Blood. 119:3321 (2012).|
|Sundararajan, V., Lee, J., Singh, K., Lee I., and Suzuki, C.K. Multitasking in the mitochondrion by the ATP-dependent Lon protease. Biochim. Biophys. Acta. Invited review on AAA+ proteins. 1823(1):56 (2012).|
|Chen S.H., C.K. Suzuki and S.H. Wu, Thermodynamic Characterization of Specific Interactions between Human Lon Protease and G-quartet DNA. Nucl. Acids Res. 36:1273 (2008).|
|Lu, B., Yadav, S., Shah, P.G., Liu, T., Tian, B., Pukszta, S., Villaluna, N., Kutejová, E., Newlon, C.S., Santos, J.H., and C.K. Suzuki. Roles for the human ATP-dependent Lon protease in mitochondrial DNA maintenance. J. Biol. Chem. 282:17363 (2007).|
|Lu, B., N. Garrido, J.N. Spelbrink and C.K. Suzuki. Tid1 isoforms are mitochondrial DnaJ-like proteins with unique carboxy-termini that determine cytosolic fate. J. Biol. Chem. 281:13150 (2006).|
|Ondrovicová, G., T. Liu, K. Singh, B. Tian, H. Li, O. Gakh, D. Perecko, J. Janata, Z. Granot, J. Orly, E. Kutejová and C.K. Suzuki. Cleavage site selection within a folded substrate by the mitochondrial ATP-dependent Lon protease. J. Biol. Chem. 280:25103 (2005).|
|Stahlberg, H., E. Kutejova, K. Suda, B. Wolpensinger, A. Lustig, G. Schatz, A. Engel, C.K. Suzuki. Mitochondrial Lon of Saccharomyces cerevisiae is a ring-shaped protease with seven flexible subunits. Proc. Natl. Acad. Sci., USA 96: 6787- 6790 (1999).|
|Rep, M., J.M. van Dijl, K. Suda, G. Schatz, L.A. Grivell and C.K. Suzuki, Promotion of mitochondrial membrane complex assembly by a proteolytically inactive yeast Lon. Science, 274 : 103-106 (1996).|
The major research area of our lab is mitochondrial biogenesis; we are investigating the regulation of mitochondrial DNA (mtDNA) stability and expression as well as the link between mitochondria and signaling pathways in cell growth and programmed cell death. Our attention is primarily focused on the mitochondrial ATP-dependent Lon protease and the mitochondrial DnaJ-like chaperone Tid1. We have shown that Lon is a unique protease that not only selectively degrades misfolded, unassembled and oxidatively damaged proteins but it also binds to DNA and RNA with sequence-specificity. Our aim is to elucidate the function of Lon in mtDNA metabolism and the quality control of mitochondrial protein biogenesis.
Tid1 is a human homolog of the Drosophila melanogaster tumor suppressor Tid56 and belongs to the family of DnaJ-like chaperones. In flies, mutations in Tid56 cause lethal tumors. In human cells, overproduction of Tid1 blocks the ability of cancer cell lines to grow in a soft agar medium, which is a characteristic of malignant cancers. By contrast, the depletion of Tid1 using RNA interference results in cell lines that are resistant to apoptotic inducing agents. Tid1 has both mitochondrial and non-mitochondrial functions. In mitochondria, we are examining the role of Tid1 in protein folding and mtDNA metabolism. Outside mitochondria, Tid1 is involved in modulating IFN-gamma signaling. Our recent work demonstrates that cellular levels of Tid1 regulate the nuclear-cytoplasmic trafficking of Stat1 (Signal transducer and activator of transcription 1). Our goal is to investigate the potential tumor suppressor activity of Tid1 and to determine whether this activity is linked to its mitochondrial function, its non-mitochondrial function or both.