Maik Hüttemann, PhD

Maik Hüttemann, PhD
Professor of Molecular Medicine and Genetics and of Biochemistry, Microbiology, and Immunology 
Division Director for Research, CMMG
Scott Hall, Rm 3214
540 E. Canfield Avenue
Detroit, MI 48201
313-577-9150
mhuttema@wayne.edu

Education

Philipps University of Marburg, Germany, PhD, 1999

Research Focus

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, mediated through cell signaling, 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) ischemia-reperfusion injury as seen in strokes and
heart attacks 3) cancer; 4) regulation including 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; and, finally 6) we have discovered
specific wavelengths of infrared light that are absorbed by COX and make it possible for the first
time to noninvasively control mitochondrial function under conditions of acute stress, such as
ischemia-reperfusion injury as seen in stroke and other tissue injuries with a first clinical trial
starting within a year.

Mentoring

Accepting new M.S. students in 2023/2024

Not accepting new Ph.D. students in 2023/2024

Recent Publications

To view a full list of Dr. Hüttemann's publications please follow this link. 

Arroum, T., Hish, G. A., Burghardt, K. J., Ghaloush, M., Bazzi, B., Mrech, A., Morse, P. T., Britton, S. L., Koch, L. G., McCully, J. D., #Hüttemann, M.,  #Malek M. H. (2024) Mitochondria transplantation: rescuing innate muscle bioenergetic impairment in a model of aging and exercise intolerance. J Strength Cond Res, in press. [#co-senior authors] 
Note: This manuscript was given The Gary A. Dudley Memorial Paper: Scientific Manuscript Excellence Designation.

Arroum, T., Pham, L., Raisanen, T.E., Morse, P.T., Wan, J., Bell, J., Lax, R., Saada, A., #Hüttemann, M., # Weksler-Zangen, S. (2024) High Sucrose Diet-Induced Subunit I Tyrosine 304 Phosphorylation of Cytochrome c Oxidase Leads to Liver Mitochondrial Respiratory Dysfunction in the Cohen Diabetic Rat Model. Antioxidants, 13(1), 19; https://doi.org/10.3390/antiox13010019. [ # co-senior authors]

Morse P.T, T. Arroum, J. Wan, L. Pham, A. Vaishnav, J. Bell, L. Pavelich, M. H. Malek, T. H. Sanderson, B. F.P. Edwards, and Hüttemann, M. (2024) Phosphorylations and Acetylations of Cytochrome c Control Mitochondrial Respiration, Mitochondrial Membrane Potential, Energy, ROS, and Apoptosis, Cells, 13(6):493. doi: 10.3390/cells13060493.

Wider, J.M., Gruley, E., Morse, P.T., Wan, J., Lee, I., Anzell, A.R., Fogo, G.M., Mathieu, J., Hish, G., O'Neil, B., Neumar, R.W., Przyklenk, K., #Hüttemann, M., # Sanderson, T.H. Modulation of mitochondrial function with near-infrared light reduces brain injury in a translational model of cardiac arrest. Crit Care, 2023;27(1):491. doi: 10.1186/s13054-023-04745-7. [ # co-senior authors]

Morse, P.T., Pérez-Mejías, G., Wan, J., Turner, A.A., Márquez, I., Kalpage, H.A., Vaishnav, A., Zurek, M.P., Huettemann, P.P., Kim, K., Arroum, T., De la Rosa, M.A., Chowdhury, D.D., Lee, I., Brunzelle, J.S., Sanderson, T.H., Malek, M.H., Meierhofer, D., Edwards, B. F.P, Díaz-Moreno, I, Hüttemann, M. Cytochrome c Lysine Acetylation Regulates Cellular Respiration and Cell Death in Ischemic Skeletal Muscle. (2023) Nat. Comm., 14(1):4166. doi: 10.1038/s41467-023-39820-8 

Morse, P.T., Tuck, S., Kerns, M., Goebel, D.J., Wan, J., Waddell, T., Wider, J.M., Hüttemann, C.L., Malek, M.H., Lee, I., Sanderson, T.H., Hüttemann, M. (2023) Non-invasive treatment of ischemia/reperfusion injury: Effective transmission of therapeutic near infrared light into the human brain through soft skin-conforming silicone waveguides. Bioeng Transl Med, 8(3):e10496 https://doi.org/10.1002/btm2.10496 

Tomasina, F., Martinez, J., Zeida, A., Chiribao, M. L., Demicheli, V., Correa, A., Quijano, C., Castro, L., Carnahan, R. H., Vinson, P., Goff, M., Cooper, T., McDonald, W. H., Castellana, N., Hannibal, L., Morse, P. T., Wan, J., Hüttemann, M., Jemmerson, R., Piacenza, L., and Radi, R. (2022) De novo sequencing and construction of a unique antibody for the recognition of alternative conformations of cytochrome c in cells. Proc Natl Acad Sci USA 119, e221343211910.1073/pnas.2213432119

Hege Hurrish, K., Qiao, X., Li, X., Su, Y., Carter, J., Ma, J., Kalpage, H. A., Hüttemann, M., Edwards, H., Wang, G., Kim, S., Dombkowski, A., Bao, X., Li, J., Taub, J. W., and Ge, Y. (2022) Co-targeting of HDAC, PI3K, and Bcl-2 results in metabolic and transcriptional reprogramming and decreased mitochondrial function in acute myeloid leukemia. Biochem Pharmacol 205, 115283 10.1016/j.bcp.2022.115283

Fu, Z., Kim, H., Morse, P. T., Lu, M. J., Hüttemann, M., Cambronne, X. A., Zhang, K., and Zhang, R. (2022) The mitochondrial NAD(+) transporter SLC25A51 is a fasting-induced gene affecting SIRT3 functions. Metabolism 135, 155275 10.1016/j.metabol.2022.155275

Wadgaonkar, P., Bi, Z., Wan, J., Fu, Y., Zhang, Q., Almutairy, B., Zhang, W., Qiu, Y., Thakur, C., Hüttemann, M., Chen, F. (2022) Arsenic Activates the ER Stress-Associated Unfolded Protein Response via the Activating Transcription Factor 6 in Human Bronchial Epithelial Cells. Biomedicines, 10(5):967. doi: 10.3390/biomedicines10050967

LaMoia, T.E., Butrico, G.M., Kalpage, H.A., Goedeke, L., Hubbard, B.T., Vatner, D.F., Gaspar, R.C., Zhang, X-M., Cline, G.W., Nakahara, K., Woo, S., Shimada, A., Hüttemann, M., and Shulman, G.I. (2022) Metformin, phenformin, and galegine inhibit complex IV activity and reduce glycerol-derived gluconeogenesis Proc. Natl. Acad. Sci. USA, 119 (10), e2122287119.

Bazylianska, V., Kalpage, H.A., Wan, J., Vaishnav, A., Mahapatra, G., Turner, A.A., Chowdhury, D.D., Kim, K., Morse, P.T., Lee, I., Brunzelle, J.S., Polin, L., Subedi, P., Heath, E.I., Podgorski, I., Marcus, K., Edwards, B.F.P., Hüttemann, M. (2021) Lysine 53 Acetylation of Cytochrome c in Prostate Cancer: Warburg Metabolism and Evasion of Apoptosis. Cells, 10(4):802. doi: 10.3390/cells10040802.

Salsaa, M., Aziz, K., Lazcano, P., Schmidtke, M.W., Tarsio, M., Hüttemann, M., Reynolds, C.A., Kane, P.M., Greenberg, M.L. (2021) Valproate activates the Snf1 kinase in Saccharomyces cerevisiae by decreasing the cytosolic pH. J Biol Chem; 297(4):101110. doi: 10.1016/j.jbc.2021.101110.

Lee, H., Jiang, X., Perwaiz, I., Yu, P., Wang, J., Wang, Y., Hüttemann, M., Felder, R.A., Sibley, D.R., Polster, B.M., Rozyyev, S., Armando, I., Yang, Z., Qu, P., Jose, P.A. (2021) Dopamine D5 receptor-mediated decreases in mitochondrial reactive oxygen species production are cAMP and autophagy dependent. Hypertens Res. doi: 10.1038/s41440-021-00646-w.

Shah, E.J., Hüttemann, M., Sanderson, T.H., Gurdziel, K., Ruden, D.M. (2021) Inhibiting Mitochondrial Cytochrome c Oxidase Downregulates Gene Transcription After Traumatic Brain Injury in Drosophila. Front. Physiol. 12:628777. doi: 10.3389/fphys.2021.628777

Morse, P.T., Goebel, D.J., Wan, J., Tuck, S., Hakim, L., Hüttemann, C.L., Malek M.H., Lee, I., Sanderson, T.H., Hüttemann, M. (2021) Cytochrome c oxidase-modulatory near-infrared light penetration into the human brain: Implications for the noninvasive treatment of ischemia/reperfusion injury. IUBMB Life, 73(3):554-567. doi: 10.1002/iub.2405.

Kalpage, H.A., Wan, J., Morse, P.T., Lee, I., Hüttemann, M. (2020) Brain-Specific Serine-47 Modification of Cytochrome c Regulates Cytochrome c Oxidase Activity Attenuating ROS Production and Cell Death: Implications for Ischemia/Reperfusion Injury and Akt Signaling. Cells, 9(8):E1843. doi: 10.3390/cells9081843. 

Liu., F., Kalpage, H.A., Wang, D., Edwards, H., Hüttemann, M., Ma, J., Su, Y., Carter, J., Li, X., Polin, L., Kushner, J., Dzinic, S.H., White, K., Wang, G., Taub, J.W., Ge, Y. (2020) Cotargeting of Mitochondrial Complex I and Bcl-2 Shows Antileukemic Activity against Acute Myeloid Leukemia Cells Reliant on Oxidative Phosphorylation. Cancers (Basel) 12(9): 2400. doi: 10.3390/cancers12092400.

Salsaa, M., Pereira, B., Liu, J., Yu, W., Jadhav, S., Hüttemann, M., Greenberg, M.L. (2020) Valproate inhibits mitochondrial bioenergetics and increases glycolysis in Saccharomyces cerevisiae. Sci Rep, 10(1):11785. doi: 10.1038/s41598-020-68725-5. 

Li, Y., Lou, W., Grevel, A., Böttinger, L., Liang, Z., Ji, J., Patil, V.A., Liu, J., Ye, C., Hüttemann, M., Becker, T., Greenberg, M.L. (2020) Cardiolipin-deficient cells have decreased levels of the iron-sulfur biogenesis protein frataxin. J Biol Chem, 295(33):11928-11937. 

Strubakos, C.D., Malik, M., Wider, J.M., Lee, I., Mitsias, P., *Hüttemann, M., *Sanderson, T.H. (2020) Non-invasive treatment with near-infrared light: A novel mechanisms-based strategy that evokes sustained reduction in brain injury after stroke.  J Cereb Blood Flow Metab, 40(4):833-844.                               

Erickson, R. P., Aras, S., Purandare, N., Hüttemann, M., Liu, J., Dragotto, J., Fiorenza, M. T., and Grossman, L. I. (2020) Decreased membrane cholesterol in liver mitochondria of the point mutation mouse model of juvenile Niemann-Pick C1, Npc1(nmf164). Mitochondrion 51, 15-21

Moreno-Domínguez, A., Ortega-Sáenz, P., Gao, L., Colinas, O., García-Flores, P., Bonilla-Henao, V., Aragonés, J., Hüttemann, M., Grossman, L.I., Weissmann, N., Sommer, N., López-Barneo, J. (2020) Acute O2 sensing through HIF2a-dependent expression of atypical cytochrome oxidase subunits in arterial chemoreceptors. Sci Signal, (13), eaay9452.

Dekhne A.S., Ning C., Nayeen, M.J., Shah, K., Kalpage, H.A., Fruhauf, J., Wallace-Povirk, A., O'Connor, C., Hou, Z., Kim, S., Hüttemann, M., Gangjee, A., Matherly, L.H. (2020) Cellular pharmacodynamics of a novel pyrrolo[3,2-d]pyrimidine inhibitor targeting mitochondrial and cytosolic one-carbon metabolism. Mol Pharmacol, 97(1):9-22.