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RIPK1 regulates starvation resistance by modulating aspartate catabolism
- Source :
- Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021), Nature Communications
- Publication Year :
- 2021
- Publisher :
- Nature Portfolio, 2021.
-
Abstract
- RIPK1 is a crucial regulator of cell death and survival. Ripk1 deficiency promotes mouse survival in the prenatal period while inhibits survival in the early postnatal period without a clear mechanism. Metabolism regulation and autophagy are critical to neonatal survival from severe starvation at birth. However, the mechanism by which RIPK1 regulates starvation resistance and survival remains unclear. Here, we address this question by discovering the metabolic regulatory role of RIPK1. First, metabolomics analysis reveals that Ripk1 deficiency specifically increases aspartate levels in both mouse neonates and mammalian cells under starvation conditions. Increased aspartate in Ripk1−/− cells enhances the TCA flux and ATP production. The energy imbalance causes defective autophagy induction by inhibiting the AMPK/ULK1 pathway. Transcriptional analyses demonstrate that Ripk1−/− deficiency downregulates gene expression in aspartate catabolism by inactivating SP1. To summarize, this study reveals that RIPK1 serves as a metabolic regulator responsible for starvation resistance.<br />RIPK1 is critical for normal development and cell death. Here, the authors identify a metabolic role for RIPK1 in aspartate homeostasis, as increased aspartate levels in RIPK1-deficient cells inhibits starvation-induced autophagy by ULK1.
- Subjects :
- Programmed cell death
Aspartate homeostasis
endocrine system diseases
Cell Survival
Sp1 Transcription Factor
Science
Citric Acid Cycle
General Physics and Astronomy
Biology
AMP-Activated Protein Kinases
General Biochemistry, Genetics and Molecular Biology
Article
Cell Line
RIPK1
Mice
Adenosine Triphosphate
medicine
Autophagy
Animals
Autophagy-Related Protein-1 Homolog
Humans
Metabolomics
Starvation
Cell Nucleus
Aspartic Acid
Multidisciplinary
Catabolism
Autophagosomes
AMPK
nutritional and metabolic diseases
General Chemistry
ULK1
Cell biology
Animals, Newborn
Receptor-Interacting Protein Serine-Threonine Kinases
medicine.symptom
hormones, hormone substitutes, and hormone antagonists
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 12
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....c0054cbe3d6778d306a299c769a146c5