Our research lies in the broad area of the molecular mechanisms that underlie metabolic homeostasis and its relationship to cell growth control. We have discovered a signaling pathway comprising the protein kinase GSK3, acetyltransferase TIP60, and protein kinase ULK1, which activates autophagy in cells deprived of serum, elucidating the molecular mechanism linking nutritional starvation to autophagy. We have also revealed that the ULK kinases phosphorylate multiple glycolytic enzymes and regulate glucose metabolic fluxes dependently of autophagy.
The main focus of our research has also been on the mechanisms for the regulation of the AMP-activated protein kinase. We have shown that the lowenergy signal AMP can autonomously initiate assembly of an activating complex for the energy sensor kinase AMPK, in that the scaffold protein AXIN tethers LKB1 to AMPK. Moreover, we have found that the AXIN/LKB1/AMPK complex and mTORC1 inversely utilize the common v-ATPaseRagulator complex for activation on the surface of lysosome, thereby uncovering a switch between anabolism and catabolism. We are exploring further how AMPK and its activating kinase LKB1 are regulated and the biological functions of these kinases.
1. Lin SY, Zhang CS, Lin SC*. Carbohydrates: Not All That Bad? Cell Metabolism. 2018 November 6;28:671-672.
2. Luo H#, Jiang M#, Lian G, Liu Q, Shi M, Li TY, Song L, Ye J, He Y, Yao L, Zhang C, Lin ZZ, Zhang CS, Zhao TJ, Jia WP, Li P, Lin SY*,Lin SC*. AIDA Selectively Mediates Downregulation of Fat Synthesis Enzymes by ERAD to Retard Intestinal Fat Absorption and Prevent Obesity.Cell Metabolism. 2018 Apr 3;27(4):843-853.e6. doi: 10.1016/j.cmet. 2018.02.021.
3. Lin SC*, Hardie DG*. AMPK: Sensing Glucose as well as Cellular Energy Status.Cell Metabolism.2018 Feb 6;27(2):299-313. doi: 10.1016/j.cmet. 2017.10.009. Epub 2017 Nov 16. (Review)
4. Zhang CS#, Hawley SA#, Zong Y#, Li M#, Wang Z, Gray A, Ma T, Cui J, Feng JW, Zhu M, Wu YQ, Li TY, Ye Z, Lin SY, Yin H, Piao HL, Hardie DG*,Lin SC*. Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK.Nature. 2017 Aug 3;548(7665):112-116. doi: 10.1038/nature23275. Epub 2017 Jul 19.
5. Zhang CS#, Li M#, Ma T#, Zong Y, Cui J, Feng JW, Wu YQ, Lin SY,Lin SC*. Metformin Activates AMPK through the Lysosomal Pathway.Cell Metabolism. 2016 Oct 11;24(4):521-522. doi: 10.1016/j.cmet. 2016.09.003.
6. Zhang CS#,Lin SC*. AMPK Promotes Autophagy by Facilitating Mitochondrial Fission.Cell Metabolism. 2016 Mar 8;23(3):399-401. doi: 10.1016/j.cmet. 2016.02.017.
7. Li TY#, Sun Y, Liang Y, Liu Q, Shi Y, Zhang CS, Zhang C, Song L, Zhang P, Zhang X, Li X, Chen T, Huang HY, He X, Wang Y, Wu YQ, Chen S, Jiang M, Chen C, Xie C, Yang JY, Lin Y, Zhao S, Ye Z, Lin SY, Chiu DT,Lin SC*. ULK1/2 Constitute a Bifurcate Node Controlling Glucose Metabolic Fluxes in Addition to Autophagy.Moleculer Cell. 2016 May 5;62(3):359-370. doi: 10.1016/j.molcel. 2016.04.009.
8. Zhang CS#, Jiang B#, Li M#, Zhu M, Peng Y, Zhang YL, Wu YQ, Li TY, Liang Y, Lu Z, Lian G, Liu Q, Guo H, Yin Z, Ye Z, Han J, Wu JW, Yin H, Lin SY,Lin SC*. The lysosomal v-ATPase-Ragulator complex is a common activator for AMPK and mTORC1, acting as a switch between catabolism and anabolism.Cell Metabolism. 2014 Sep 2;20(3):526-40. doi: 10.1016/j.cmet. 2014.06.014. Epub 2014 Jul 4
9. Zhang YL#, Guo H#, Zhang CS#, Lin SY, Yin Z, Peng Y, Luo H, Shi Y, Lian G, Zhang C, Li M, Ye Z, Ye J, Han J, Li P, Wu JW,Lin SC*. AMP as a low-energy charge signal autonomously initiates assembly of AXIN-AMPK-LKB1 complex for AMPK activation.Cell Metabolism. 2013 Oct 1;18(4):546-55. doi: 10.1016/j.cmet. 2013.09.005.
10. Lin SY#, Li TY#, Liu Q, Zhang C, Li X, Chen Y, Zhang SM, Lian G, Liu Q, Ruan K, Wang Z, Zhang CS, Chien KY, Wu J, Li Q, Han J,Lin SC*. GSK3-TIP60-ULK1 signaling pathway links growth factor deprivation to autophagy.Science. 2012 Apr 27;336(6080):477-81. doi: 10.1126/science.1217032.