SOD1 Phosphorylation by mTORC1 Couples Nutrient Sensing and Redox Regulation.

Abstract:

: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.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Tsang CK,Chen M,Cheng X,Qi Y,Chen Y,Das I,Li X,Vallat B,Fu LW,Qian CN,Wang HY,White E,Burley SK,Zheng XFS

doi

10.1016/j.molcel.2018.03.029

subject

Has Abstract

pub_date

2018-05-03 00:00:00

pages

502-515.e8

issue

3

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(18)30232-6

journal_volume

70

pub_type

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