SOD1 Phosphorylation by mTORC1 Couples Nutrient Sensing and Redox Regulation.
Nutrients are not only organic compounds fueling bioenergetics and biosynthesis, but also key chemical signals controlling growth and metabolism. Nutrients enormously impact the production of reactive oxygen species (ROS), which play essential roles in normal physiology and diseases. How nutrient signaling is integrated with redox regulation is an interesting, but not fully understood, question. Herein, we report that superoxide dismutase 1 (SOD1) is a conserved component of the mechanistic target of rapamycin complex 1 (mTORC1) nutrient signaling. mTORC1 regulates SOD1 activity through reversible phosphorylation at S39 in yeast and T40 in humans in response to nutrients, which moderates ROS level and prevents oxidative DNA damage. We further show that SOD1 activation enhances cancer cell survival and tumor formation in the ischemic tumor microenvironment and protects against the chemotherapeutic agent cisplatin. Collectively, these findings identify a conserved mechanism by which eukaryotes dynamically regulate redox homeostasis in response to changing nutrient conditions.
['Tsang|Chi Kwan|CK|', 'Chen|Miao|M|', 'Cheng|Xin|X|', 'Qi|Yanmei|Y|', 'Chen|Yin|Y|', 'Das|Ishani|I|', 'Li|Xiaoxing|X|', 'Vallat|Brinda|B|', 'Fu|Li-Wu|LW|', 'Qian|Chao-Nan|CN|', 'Wang|Hui-Yun|HY|', 'White|Eileen|E|', 'Burley|Stephen K|SK|', 'Zheng|X F Steven|XFS|']
D000818:Animals D002460:Cell Line D045744:Cell Line, Tumor D004249:DNA Damage D004734:Energy Metabolism D005260:Female D057809:HEK293 Cells D006801:Humans D061986:MCF-7 Cells D000076222:Mechanistic Target of Rapamycin Complex 1 D008807:Mice, Inbred BALB C D008819:Mice, Nude D000078622:Nutrients D010084:Oxidation-Reduction D010766:Phosphorylation D017382:Reactive Oxygen Species D015398:Signal Transduction D000072105:Superoxide Dismutase-1 D058570:TOR Serine-Threonine Kinases
nutrient redox reactive oxygen species superoxide dismutase 1 rapamycin cancer cisplatin Warburg ischemia mTOR