Steven E. Glynn, Ph.D.

Associate Professor
Department of Biochemistry and Cell Biology

148 Centers for Molecular Medicine
Stony Brook University
Stony Brook, NY 11794-5115

Office telephone: 631-632-1055
E-mail: steven.glynn@stonybrook.edu

Lab Page

• Research Description

  Mechanisms of Proteostasis in Mitochondria

  Proteases provide spatio-temporal control of biological processes by destroying critical protein components at precise times.  Understanding how proteases select proteins substrates from a crowded cellular environment and catalyze their degradation is crucial to making sense of how biological processes are regulated. Controlled protein degradation is essential for maintaining the function of mitochondria. ATP production, calcium signalling, fatty acid metabolism, and programmed cell death are all regulated by a mitochondrial proteome that is largely encoded in the nucleus and imported into the organelle.

  A major topic of interest in the lab is the role that energy-dependent proteases belonging to the AAA+ family of enzymes play in sculpting the mitochondrial proteome. We are focused on determining the rules that govern substrate selection by these proteases and the conformational fluctuations that allow them to capture energy from ATP hydrolysis to be used in protein degradation.

• Publications

  Steele, T.E and Glynn, S.E. Mitochondrial AAA proteases: a stairway to degradation. (2019). Mitochondrion. 49, 121-127.

  Puchades, C.*, Ding, B.*, Song, A., Wiseman, R.L., Lander, G.C., Glynn, S.E. Unique structural features of the mitochondrial AAA+ protease AFG3L2 reveal the molecular basis for activity in health and disease. (2019). Molecular Cell. 75, 1073-1085. *co-first authors

  Elmes, M.W., Prentis, L.E., McGoldrick. L.L., Giuliano, C.J., Sweeney, J.M., Joseph, O.M., Che, J., Carbonetti, G.S., Studholme, K., Deutsch, D.G., Rizzo, R.C., Glynn, S.E., Kaczocha, M. (2019). FABP1 controls hepatic transport and biotransformation of D9-THC. Scientific Reports,

  Ding, B., Martin, D.W., Rampello, A.J., Glynn, S.E. (2018). Dissecting Substrate Specificities of the Mitochondrial AFG3L2 Protease. Biochemistry. 57, 4225-4235. 9, 7588.

  Puchades, C., Rampello, A.J., Shin, M., Giuliano, C.J., Wiseman, R.L., Glynn, S.E., Lander, G.C. (2017). Structure of the mitochondrial inner membrane AAA+ protease YME1 gives insight into substrate processing. Science, 358, 6363.

  Glynn, S.E. (2017). Multifunctional mitochondrial AAA proteases. Frontiers in Molecular Biosciences. 4:34.

  Baytshtok V., Chen J., Glynn S.E., Nager A.R., Grant R.A., Baker T.A. and Sauer R.T. (2017). Covalently linked HslU hexamers support a probabilistic mechanism that links ATP hydrolysis to protein unfolding and translocation. Journal of Biological Chemistry. 292, 56965-5704.

  Rampello, A.J. and Glynn, S.E. (in press). Identification of a degradation signal within substrates of the mitochondrial i-AAA protease. Journal of Molecular Biology.

  Shi H., Rampello A.J., Glynn S.E. (2016). Engineered AAA+ proteases reveal principles of proteolysis at the mitochondrial inner membrane. Nat. Commun., 7, 13301.

  Glynn S.E., Chien P. (2016). Sending protein aggregates into a downward spiral. Nat. Struct. Mol. Biol., 23, 769-70.

  Sirrs S., van Karnebeek C.D., Peng X., Shyr C., Tarailo-Graovac M., Mandal R., Testa D., Dubin D., Carbonetti G., Glynn S.E., Sayson B., Robinson W.P., Han B., Wishart D., Ross C.J., Wasserman W.W., Hurwitz T.A., Sinclair G., Kaczocha M. (2015). Defects in fatty acid amide hydrolase 2 in a male with neurologic and psychiatric symptoms. Orphanet J Rare Dis., 28, 10-38.

  Stinson BM, Nager AR, Glynn SE, Schmitz KR, Baker TA, Sauer RT. (2013). Nucleotide binding and conformational switching in the hexameric ring of a AAA+ machine. Cell, 153, 628-39.

  Glynn, S.E., Nager, A.R., Baker, T.A. and Sauer, R.T. (2012). Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine. Nat. Struct. Mol. Biol., 19, 616-622.

  Glynn, S.E., Martin, A., Nager, A.R., Baker, T.A. and Sauer R.T. (2009). Structures of asymmetric ClpX hexamers reveal nucleotide-dependent motions in a AAA+ protein-unfolding machine. Cell, 139, 744-756.

  Glynn S.E., Baker P.J., Sedelnikova S.E., Davies C.L., Eadsforth T.C., Levy C.W., Rodgers H.F., Blackburn G.M., Hawkes T.R., Viner R. and Rice D.W. (2005). Structure and mechanism of imidazole-glycerol phosphate dehydratase., Structure,13, 1807-1817.

  Glynn, S.E., Baker, P.J., Sedelnikova, S.E., Levy, C.W., Rodgers, H.F., Blank, J.,Hawkes, T.R. and Rice, D.W. (2005). Purification, crystallization and preliminary crystallographic analysis of Arabidopsis thaliana imidazoleglycerol-phosphate dehydratase. Acta Crystallogr. Sect. F, 61, 776-778.

  Hartley, A., Glynn, S.E., Barynin, V., Baker, P.J., Sedelnikova, S.E., Verhees, C.H., de Geus, D., van der Oost, J., Timson, D.J., Reece, R.J., Rice, D.W. (2004). Substrate specificity and mechanism from the structure of Pyrococcus furiosus galactokinase. J. Mol. Biol., 337, 387-398.

  De Geus, D., Hartley, A., Sedelnikova, S.E., Glynn, S.E., Baker, P.J., Verhees, C.H., van der Oost, J. and Rice, D.W. (2003). Cloning, purification, crystallization and preliminary crystallographic analysis of galactokinase from Pyrococcus furiosus. Acta Crystallogr. Sect D, 59, 1819-1821.