|Maik Hüttemann, Ph.D.
3214 Scott Hall
540 East Canfield
Detroit, MI 48201
|Associate Professor; Ph.D., Marburg (Germany), 1999. Regulation of cytochrome c oxidase and cytochrome c, oxygen sensing, cell signaling to the mitochondria, and role of mitochondria in cancer.
Research InterestsMitochondria 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.
Yu, H., Lee, I., Salomon, A.R., Yu, K., Huttemann, M. (2008) Mammalian liver cytochrome c is tyrosine-48 phosphorylated in vivo, inhibiting mitochondrial respiration, Biochim Biophys Acta - Bioenergetics, 1777 (7-8), 1066-71
Samavati, L., Lee, I., Mathes, I., Lottspeich, F., Huttemann, M. (2008) TNF? Inhibits Oxidative Phosphorylation through Tyrosine Phosphorylation at Subunit I of Cytochrome c Oxidase, J Biol Chem, 283 (30), 21134-44
Hüttemann, M., I. Lee, A. Pecinova, P. Pecina, K. Przyklenk, and J.W. Doan (2008) Regulation of oxidative phosphorylation, the mitochondrial membrane potential, and their role in human disease. J Bioenerg Biomembr, 40(5): 445-56.
Rastogi, R., Du, W., Hüttemann, M., Fite, A. Franchi, L., Samavati, L. (2009) STAT3 tyrosine phosphorylation is critical for interleukin 1-beta and interleukin-6 production in response to lipopolysaccharide and live bacteria. Molecular Immunology, 46(8-9),1867-77.
Lee, I., Salomon, A.R., Yu, K., Samavati, L., Pecina, P., Pecinova, A., Hüttemanna, M. (2009) Isolation of regulatory-competent, phosphorylated cytochrome c oxidase. Methods Enzymol, 457:193-210.
Acsadi, G., Lee, I., Li, X.,; Khaidakov, M., Pecinova, A., Parker, G., Hüttemann, M. (2009) Mitochondrial dysfunction in a neural cell model of spinal muscular atrophy. J Neurosci Res, 87:2748-56.
Hüttemann, M., Zhang, Z., Mullins, C., Bessert, D., Lee, I., Armin-Narve, K., Skoff, R.P. (2009) Different proteolipid protein mutants exhibit unique metabolic defects, ASN Neuro 1(3): 165-180.
Demory, M.L., Julie L., Boerner, J.L., Davidso, R., Faust, W.,Miyake, T., Lee, I., Hüttemann, M., Douglas, R. Haddad, G., Parsons, S.J. (2009) Epidermal Growth Factor Receptor Translocation to the Mitochondria: Regulation and Effect, J Biol Chem, 284(52): 36592-604.
Lee, I., Pecinova, A., Pecina, P., Neel, B., Kucherlapati, R., Roberts, A., Hüttemann, M. (2010) A suggested role for mitochondria in Noonan syndrome, Biochim Biophys Acta Molecular Basis of Disease, 1802: 275-83.
Hüttemann, M., Nantwi, K.D., Lee, I., Liu, J., Mohiuddin, S., Petrov, T. (2010) Theophylline treatment improves mitochondrial function after upper cervical spinal cord hemisection. Experimental Neurology, 223(2): 523-8.
Barnes, V.L., Strunk, B.S., Lee, I., Hüttemann, M., Pile, L.A. (2010) Loss of the SIN3 Transcriptional Corepressor Results in Aberrant Mitochondrial, BMC Biochemistry, 11(21):1-12.
Pecina, P., Borisenko, G.G., Belikova, N.A., Tyurina, Y.Y., Pecinova, A., Lee, I., Samhan-Arias, A.K., Przyklenk, K., Kagan, V.E., Hüttemann, M. (2010) Phosphomimetic substitution of cytochrome c tyrosine 48 decreases respiration and binding to cardiolipin, and abolishes ability to trigger downstream caspase activation. Biochemistry, 9(31):6705-14.