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    ULK1-Sestrin2 Signaling Pathway in Mammalian Autophagy Induction

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    SÉMINAIRE DE L'INSTITUT COCHIN

    Seung-Hyun Ro 

    Seung-Hyun Ro

    Department of Biochemistry, University of Nebraska-Lincoln, USA

     

    Mardi 23 mai 2017 à 12h00

     

     invité par Benoit Viollet

     

    Institut Cochin, 22 rue Méchain, 75014 Paris
    Salle de conférence Rosalind Franklin, 2e étage

    Dr. Seung-Hyun Ro is an assistant professor of Biochemistry at University of Nebraska-Lincoln. Prior to joining UNL, he was a research scientist at University of Michigan Medical School and Cornell University. He holds a PhD from University of Minnesota-Twin Cities and a BS/MS from KAIST in South Korea. Dr Ro’s research interests are Sestrins-regulated metabolic signaling and autophagy-mediated adaptation of various stress conditions in obesity and cancer. One of the main interests of his lab is understanding Sestrins' role in lipid metabolism, mTORC1 signaling and Redox biology. Currently, his lab is focusing on the biology of white adipose tissue (WAT) and brown adipose tissue (BAT) - the impact of oxidative stress in adipose metabolism and the regulation of autophagy by Sestrins in overnutrition stress.
    Sestrins (Sestrin1, 2 and 3) are a family of stress-inducible proteins that regulate metabolism. Sestrins have an antioxidant function that suppresses reactive oxygen species (ROS). Sestrins activate AMP-activated protein kinase (AMPK), inhibiting mechanistic target of rapamycin complex 1 (mTORC1). Upregulation of mTORC1 has been shown to lead to the accelerated development of several age-related and obesity-induced pathologies, such as lipid accumulation, mitochondrial dysfunction, protein aggregate formation, cardiac arrhythmia and muscle degeneration. These pathologies were stifled by inhibition of mTORC1 and use of antioxidants, which shows that the mTORC1- and ROS-controlling functions of Sestrin are indeed important for metabolism.

    Selected publications

    • Ro SH, Xue *, Ramakrishnan SK, Cho CS, Namkoong S, Jang I, Semple IA, Ho A, Park HW, Shah YM, Lee JH. (2016) Tumor suppressive role of sestrin2 during colitis and colon carcinogenesis. Elife 5 : e12204,
    • Kim M, Sandford E, Gatica D, Qiu Y, Liu X, Zheng Y, Schulman BA, Xu J, Semple I, Ro SH, Kim B, Mavioglu RN, Tolun A, Jipa A, Takats S, Karpati M, Li JZ, Yapici Z, Juhasz G, Lee JH, Klionsky DJ, Burmeister M. (2016) Mutations in ATG5 reduces autophagy and leads to ataxia with developmental delay. Elife 5 : e12245
    • Kim H, An S, Ro SH*, Teixeira FP, Park GJ, Kim C, Cho CS, Kim JS, Jakob U, Lee JH and Cho US. (2015) Janus-faced Sestrin2 controls ROS and mTOR signaling through two separate functional domains. Nature Commun. 6 : 10025,
    • Ro SH, Semple I, Ho A, Park HW, Lee JH. (2015) Sestrin2, a Regulator of Thermogenesis andMitohormesis in Brown Adipose Tissue. Front Endocrinol (Lausanne). 6 : 114
    • Kim M, Semple I, Kim B, Kiers A, Nam S, Park HW, Park H, Ro SH, Kim JS, Juhasz G, and Lee JH.(2015) Drosophila Gyf/GRB10 interaction GYF protein is an autophagy regulator that controls neuron and muscle homeostasis. Autophagy 11 : 1358-1372
    • Kim JS, Ro SH, Kim M, Park HW, Semple IA, Park H, Cho US, Wang W, Guan KL, Karin M, Lee JH. (2015) Sestrin2 inhibits mTORC1 through modulation of GATOR complexes. Sci. Rep. 5 : 9502,
    • Park HW, Park H, Semple IA, Jang I, Ro SH, Kim M, Cazares VA, Stuenkel EL,Kim JJ, Kim JS, Lee JH. (2014) Pharmacological correction of obesity-induced autophagy arrest using calcium channel blockers. Nature Commun. 5 : 4834
    • Ro SH, Semple IA, Park H, Park HL, Park HW, Kim M, Kim JS, Lee JH. (2014) Sestrin2 Promotes Unc-51-like Kinase 1 Mediated Phosphorylation of p62/sequestosome-1. FEBS J. 281 : 3816-3827
    • Park HW, Park HL, Ro SH, Jang I, Semple IA, Kim DN, Kim M, Nam M, Zhang D, Yin L, Lee JH. (2014) Hepatoprotective role of Sestrin2 against chronic ER stress. Nature Commun. 5 : 4233
    • Ro SH, Nam M, Jang I, Park HW, Park HL, Semple IA, Kim M, Kim JS, Park H, Einat P, Damari G, Golikov M, Feinstein E, Lee JH. (2014) Sestrin2 inhibits uncoupling protein 1 expression through suppressing reactive oxygen species. Proc Natl Acad Sci U.S.A. 111 : 7849-7854 

     

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