| Assistant Professor; Ph.D., Marburg (Germany), 1999. Function of cytochrome c oxidase isoforms, oxygen sensing, and role of mitochondria in cancer.
Research Interests
Mitochondria are organelles that began as symbiotic organisms within the eukaryotic cell. They produce most biological energy (ATP) but also most of the reactive oxygen species (ROS) that can damage biological molecules, and they are a pivotal site for cellular programmed cell death (apoptosis). It is therefore not surprising that mitochondrial dysfunction is involved in most human disease, including cancer, neurodegenerative disease, ischemia, and diabetes.
Our team studies mitochondrial function using genetic and biochemical approaches. We focus on two key components of the mitochondrial oxidative phosphorylation machinery, cytochrome c oxidase (COX) and the small electron carrier cytochrome c (Cytc). COX is the terminal enzyme of the mitochondrial respiratory chain, “burns” the oxygen we breathe to water, and pumps protons across the inner mitochondrial membrane generating the mitochondrial membrane potential, which is utilized by ATP synthase to produce energy in the form of ATP. Cytc has two distinct functions: it delivers electrons to COX, but it also participates in programmed cell death (apoptosis).
The overall goal of our work is to understand the regulation of COX and Cytc in normal and disease conditions. This regulation in turn affects energy production, free radical generation, and apoptosis. Research topics of the Hüttemann group under investigation include 1) cell signaling pathways that act on COX and Cytc, which pathways are often dysregulated in human diseases; 2) lung cancer; 3) neurodegenerative diseases; 4) gene regulation of COX subunit isoforms; and 5) novel strategies to boost mitochondrial function as a future treatment for diseases that manifest themselves in a lack of energy and increased cell death.
Please also visit http://www.genetics.wayne.edu/maik/homepage.html
Selected Publications
Goldberg, A., Wildman, D.E., Schmidt, T.R., Hüttemann, M., Goodman, M., Weiss, M.L., Grossman, L.I. (2003) Adaptive evolution of cytochrome c oxidase subunit VIII in anthropoid primates. Proc Natl Acad Sci, 100, 5873-8.
Hüttemann, M., Schmidt, T.R., Grossman, L.I. (2003) A third isoform of cytochrome c oxidase subunit VIII is present in mammals. Gene, 312: 95-102
Hüttemann, M., Jaradat, S., Grossman, L.I. (2003) Cytochrome c oxidase of mammals contains a testes-specific isoform of subunit VIb - the counterpart to testes-specific cytochrome c? Mol. Reprod. Dev. 66: 8-16.
Kadenbach, B., Arnold, S., Lee, Icksoo, Hüttemann, M. (2004) The possible role of cytochrome c oxidase in stress-induced apoptosis and degenerative diseases. Biochim Biophys Acta, 1655: 400-8
Doan, J.W., Schmidt, T.R., Wildman, D.E., Uddin, M., Goldberg, A. Hüttemann, M., Goodman, M., Weiss, M.L., Grossman, L.I. (2004) Coadaptive evolution in cytochrome c oxidase: 9 of 13 subunits show accelerated rates of nonsynonymous substitution in anthropoid primates, Mol Bio Evol, 33: 944-950
Lee, I., Salomon, A.R., Ficarro, S., Mathes, I., Lottspeich, F., Grossman, L.I., Hüttemann, M (2005) cAMP-dependent Tyrosine Phosphorylation of Subunit I inhibits Cytochrome c Oxidase activity, J Biol Chem, 280: 6094-100.
Icksoo Lee, Arthur R. Salomon, Kebing Yu, Jeffrey W. Doan, Lawrence I. Grossman, L.I., Maik Hüttemann (2006) New Prospects for an Old Enzyme: Mammalian Cytochrome c is Tyrosine-Phosphorylated in Vivo, Biochemistry, 45(30): 9121-8
Hüttemann, M., Lee, I., Liu, J., Grossman, L.I. (2007) Transcription of cytochrome c oxidase subunit IV-2 is controlled by a novel oxygen responsive element conserved in mammals, FEBS Journal, 274 (21),5737-48.
Hüttemann, M., Lee, I., Samavati, L., Yu, H., Doan, J.W. (2007) Regulation of mitochondrial oxidative phosphorylation through cell signaling, BBA - Mol Cell Res, 1773: 1701–20
Duvigneau, J.C., Piskernik, C., Haindl, S., Burkhard, K., Hartl, R.T., Hüttemann, M., Lee, I., Ebel, T., Moldzio, R., Gemeiner, M., Redl, H., Kozlov, A.V. (2008) Iron ions cause mitochondrial dysfunction in liver of rats subjected to endotoxic shock: the role of heme oxygenase 1, Laboratory Investigation, 88(1): 70-7
Hüttemann, M., Lee, I., Kreipke, C.W., Petrov, T., (2008) Suppression of iNOS prior to traumatic brain injury improves cytochrome c oxidase activity and normalizes cellular energy levels, Neuroscience 151 (1): 148-54
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