Congratulations to Erin O’Leary on her 1st author publication covering her work as a technician in Dr. Gökhan Mutlu’s lab at the University of Chicago.
This work built on their previous findings that glycine is required for collagen synthesis in myofibroblasts. This paper sought to determine the role of ATF4 in this pathway. AFT4 is a regulator of amino acid metabolism. They found that primary driver of ATF4 downstream of TGF-β is activation of the Mechanistic Target of Rapamycin Complex 1 (mTORC1). They used a panel of mTOR inhibitors and found that Rapalink-1, which specifically targets the kinase domain of mTORC1, completely inhibited ATF4 induction and metabolic reprogramming downstream of TGF-β.
O’Leary, E. M., Tian, Y., Nigdelioglu, R., Witt, L. J., Cetin-Atalay, R., Meliton, A. Y., Woods, P. S., Kimmig, L. M., Sun, K. A., Gökalp, G. A., Mutlu, G. M., & Hamanaka, R. B. (2020). TGF-β Promotes Metabolic Reprogramming in Lung Fibroblasts via mTORC1-dependent ATF4 Activation. American Journal of Respiratory Cell and Molecular Biology.
DOI: 10.1165/rcmb.2020-0143OC, PMID: 32668192