Mammalian target of rapamycin complex 1 (mTORC1)-mediated phosphorylation stabilizes ISCU protein: implications for iron metabolism

The scaffold protein ISCU facilitates the assembly of iron-sulfur clusters (ISCs), which are essential cofactors for many vital metabolic processes. The mTOR pathways are central to nutrient and energy-sensing networks. Here, we demonstrate that mTORC1 associates with ISCU and phosphorylates ISCU at...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2013-05, Vol.288 (18), p.12901-12909
Main Authors: La, Ping, Yang, Guang, Dennery, Phyllis A
Format: Article
Language:English
Subjects:
3T3-L1 Cells
Animals
HeLa Cells
Homeostasis - physiology
Humans
Iron - metabolism
Iron-Sulfur Proteins - genetics
Iron-Sulfur Proteins - metabolism
Mechanistic Target of Rapamycin Complex 1
Metabolism
Mice
Multiprotein Complexes
Phosphorylation - physiology
Protein Stability
Proteins - genetics
Proteins - metabolism
TOR Serine-Threonine Kinases - genetics
TOR Serine-Threonine Kinases - metabolism
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The scaffold protein ISCU facilitates the assembly of iron-sulfur clusters (ISCs), which are essential cofactors for many vital metabolic processes. The mTOR pathways are central to nutrient and energy-sensing networks. Here, we demonstrate that mTORC1 associates with ISCU and phosphorylates ISCU at serine 14. This phosphorylation stabilized ISCU protein. Insufficiency of ISCU triggered by mTORC1 inhibition prevented ISC assembly. Sustained ISCU protein levels enhanced by mTORC1 sensitized TSC2-null cells to iron deprivation due to constitutive ISC biogenesis-triggered iron demand, which outstrips supply. We conclude that the mTORC1 pathway serves to modulate iron metabolism and homeostasis, and we speculate that iron deprivation may be an adjunct in the treatment of cancers characterized by constitutive mTORC1 activation.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M112.424499