Nathan Alder

Professor

Molecular and Cell Biology / Structural Biology, Biochemistry and Biophysics (SB3)

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Education: Ph.D., University of California, Davis; Postdoctoral study, Texas A&M University

Research Interests: Analysis of the structure, function, and biogenesis of membrane proteins using multiple techniques, primarily fluorescence spectroscopy, and employing yeast as a model system; mitochondrial protein trafficking and assembly; high-resolution fluorescence-based mapping of membrane proteins and analysis of conformational dynamics.

Selected Publications:

Wayne Mitchell, Jeffrey D Tamucci, Emery L Ng, Shaoyi Liu, Alexander V Birk, Hazel H Szeto, Eric R May, Andrei T Alexandrescu, Nathan N Alder (2022) Structure-activity relationships of mitochondria-targeted tetrapeptide pharmacological compounds eLife 11:e75531 https://doi.org/10.7554/eLife.75531

Joseph C. Iovine, Steven M. Claypool, Nathan N. Alder. (2021) Mitochondrial compartmentalization: emerging themes in structure and function, Trends in Biochemical Sciences, ISSN 0968-0004, https://doi.org/10.1016/j.tibs.2021.06.003.

Huiliang Zhang, Nathan N Alder, Wang Wang, Hazel Szeto, David J Marcinek, Peter S Rabinovitch, Reduction of elevated proton leak rejuvenates mitochondria in the aged cardiomyocyte.  eLife 2020;9:e60827 DOI: 10.7554/eLife.60827

Mitchell, W., Ng, E.A., Tamucci, J.D., Boyd, K.J., Sathappa, M., Coscia, A., Pan, M., Xan, X., Eddy, N.A., May, E.R., Szeto, H.H., and Alder, N.N. (2020) The mitochondria-targeted peptide SS-31 binds lipid bilayers and modulates surface electrostatics as a key component of its mechanism of action. Journal of Biological Chemistry 295: 7452-7469. doi: 10.1074/jbc.RA119.012094

Minkyung Bae, Yoojin Lee, Young-Ki Park, Dong-Guk Shin, Pujan Joshi, Seung-Hyun Hong, Nathan Alder, Sung I. Koo, Ji-Young Lee (2019) Astaxanthin attenuates the increase in mitochondrial respiration during the activation of hepatic stellate cells. The Journal of Nutritional Biochemistry 71 (2019) 82-89 https://doi.org/10.1016/j.jnutbio.2019.06.001

Phosphatidylethanolamine made in the inner mitochondrial membrane is essential for yeast cytochrome bc1 complex function (2019). Calzada, E., Avery, E., Sam, P.N., Modak, A., Wang, C., McCaffery, J.M., Han, X., Alder, N.N. and Claypool, S.M. Nature Communications. 29;10(1):1432. doi: 10.1038/s41467-019-09425-1

Kevin J. Boyd, Nathan N. Alder, Eric R. May. (2018)  Molecular Dynamics Analysis of Cardiolipin and Monolysocardiolipin on Bilayer Properties. BiophysicalJournal, doi.org/10.1016/j.bpj.2018.04.001.

Malhotra, K., Modak, A., Nangia, S., Daman, T.H., Gunsel, U. Robinson, V.L., Mokranjac, D., May, E.R., and Alder, N.N. (2017) Cardiolipin mediates membrane and channel interactions of the mitochondrial TIM23 protein import complex receptor Tim50. Science Advances DOI: 10.1126/sciadv.1700532

Boyd, K.K., Alder, N.N., May, E.R. (2017) Buckling Under Pressure: Curvature Based Lipid Segregation and Stability Modulation in Cardiolipin Containing Bilayers.Langmuir , DOI: 10.1021/acs.langmuir.7b01185

Malhotra, K. and Alder, N.N. (2017) Reconstitution of mitochondrial proteins into nanodiscs by cell-free expression. Methods Mol. Biol. 1567: 155-178.

Sathappa, M., and Alder, N.N. (2016) “The ionization properties of cardiolipin and its variants in model bilayers” BBA-Biomembranes [Epub ahead of print].

Lee, K.K., Imaizumi, N., Chamberland, S.R., Alder, N.N., and Boelsterli, U.A. (2014). Targeting mitochondria with methylene blue protects mice against acetaminophen-induced liver injury. Hepatology. doi: 10.1022/hep.27385.

Hwang, M.S., Schwall C.T., Pazarentzos, E., Datler, C., Alder, N.N., and Grimm, S. (2014). Mitochondrial Ca2+ influx targets cardiolipin to disintegrate respiratory chain complex II for cell death induction. Cell Death Differ. doi: 10.1038/cdd.2014.84 [Epub ahead of print].

Malhotra, K., and Alder, N.N. (2014) Advances in the use of nanoscale bilayers to study membrane protein structure and function. Biotechnol. Genet. Eng. Rev. 30:79-93. doi: 10.1080/02648725.2014.921502.

Malhotra, K., Sathappa, M., Landin, J.S., Johnson, A.E., and Alder, N.N. Structural changes in the mitochondrial Tim23 channel are coupled to the proton-motive force. Nature Structural and Molecular Biology (in press).

Schwall, C.T., and Alder, N.N. Site-specific fluorescent probe labeling of mitochondrial membrane proteins. Methods in Molecular Biology (in press).

Long, A.R., O’Brien, C.C., Malhotra, K., Schwall, C.T., Albert, A.D., Watts, A., and Alder, N.N. (2013). A detergent-free strategy for the reconstitution of active enzyme complexes from native biological membranes into nanoscale discs. BMC Biotechnology 13(1):41 (Epub ahead of print).

Long, A.R., O’Brien, C.C., and Alder, N.N. (2012). The cell-free integration of a polytopic mitochondrial membrane protein into liposomes occurs cotranslationally and in a lipid-dependent manner. PLoS One 7(9): e46332. doi:10.1371/journal.pone.0046332.

Schwall, C.T., Greenwood, V.L., and Alder, N.N. (2012). The stability and activity of respiratory Complex II is cardiolipin-dependent. Biochimica et Biophysica Acta – Bioenergetics 1817, 1588-1596.

Ranaghan, M.J., Schwall, C.T., Alder, N.N., and Birge, R.R. (2011). Green proteorhodopsin reconstituted into nanoscale phospholipid bilayers (nanodiscs) as photoactive monomers. Journal of the American Chemical Society 133, 18318-18327.

Alder, N.N., Jensen, R.E., and Johnson, A.E. (2008). Fluorescence mapping of mitochondrial TIM23 complex reveals a water-facing, substrate-interacting helix surface. Cell 134, 439-450.

Alder, N.N., Sutherland, J., Buhring, A.I., Jensen, R.E., and Johnson, A.E. (2008). Quaternary structure of the mitochondrial TIM23 complex reveals dynamic association between Tim23p and other subunits. Molecular Biology of the Cell 19, 159-170.

Davis, A.J., Alder, N.N., Jensen, R.E., and Johnson, A.E. (2007). The Tim9p/10p and Tim8p/13p complexes bind to specific sites on Tim23p during mitochondrial protein import. Molecular Biology of the Cell 18, 175-486.

Alder, N.N., Shen, Y., Brodsky, J.L., Hendershot, L.M., and Johnson, A.E. (2005). The molecular mechanisms underlying BiP-mediated gating of the Sec61 translocon of the endoplasmic reticulum. The Journal of Cell Biology 168, 389-399.

Alder, N.N. and Johnson, A.E. (2004). Cotranslational membrane protein biogenesis at the endoplasmic reticulum. The Journal of Biological Chemistry 279, 22787-22790.

Alder, N.N. and Theg, S.M. (2003). Energy use by biological protein transport pathways. Trends in Biochemical Sciences 28, 442-451.

Alder, N.N. and Theg, S.M. (2003). Energetics of protein transport across biological membranes: a study of the thylakoid ΔpH/cpTat pathway. Cell 112, 231-242.

Alder, N.N. and Theg, S.M. (2003). Protein transport via the cpTat pathway displays cooperativity and is stimulated by transport-incompetent substrate. FEBS Letters 540, 96-100.