ROS-Mediated p53 Induction of Lpin1 Regulates Fatty Acid Oxidation in Response to Nutritional Stress
- Resource Type
- Authors
- Wanli Xuan; Daniel A. Rubinger; Keith Wheaton; Wissam Assaily; Lauren Brown-Endres; Weili Ma; Katsuya Tsuchihara; Tak W. Mak; Samuel Benchimol; Yunping Lin
- Source
- Molecular Cell. 44:491-501
- Subject
- Time Factors
DNA damage
Phosphatidate Phosphatase
Nutritional Status
Cell Cycle Proteins
Ataxia Telangiectasia Mutated Proteins
Protein Serine-Threonine Kinases
Biology
Transfection
Cell Line
Myoblasts
Mice
chemistry.chemical_compound
Enzyme activator
Adipocyte
Serine
Animals
Humans
Phosphorylation
Molecular Biology
Beta oxidation
Mice, Knockout
Tumor Suppressor Proteins
Fatty Acids
Nuclear Proteins
Lipid metabolism
Cell Biology
Metabolism
DNA-Binding Proteins
Enzyme Activation
Oxidative Stress
Glucose
chemistry
Biochemistry
RNA Interference
Tumor Suppressor Protein p53
Energy Metabolism
Reactive Oxygen Species
Oxidation-Reduction
C2C12
DNA Damage
- Language
- ISSN
- 1097-2765
The p53 protein is activated by stress signals and exhibits both protective and death-promoting functions that are considered important for its tumor suppressor function. Emerging evidence points toward an additional role for p53 in metabolism. Here, we identify Lpin1 as a p53-responsive gene that is induced in response to DNA damage and glucose deprivation. Lpin1 is essential for adipocyte development and fat metabolism, and mutation in this gene is responsible for the lypodystrophy phenotype in fld mice. We show that p53 and Lpin1 regulate fatty acid oxidation in mouse C2C12 myoblasts. p53 phosphorylation on Ser18 in response to low glucose is ROS and ATM dependent. Lpin1 expression in response to nutritional stress is controlled through the ROS-ATM-p53 pathway and is conserved in human cells. Lpin1 provides a critical link between p53 and metabolism that may be an important component in mediating the tumor suppressor function of p53.