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RIPK1 regulates starvation resistance by modulating aspartate catabolism

Author

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  • Xinyu Mei

    (Chinese Academy of Sciences
    Tongji University School of Medicine)

  • Yuan Guo

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Zhangdan Xie

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yedan Zhong

    (Chinese Academy of Sciences)

  • Xiaofen Wu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Daichao Xu

    (Chinese Academy of Sciences)

  • Ying Li

    (Chinese Academy of Sciences)

  • Nan Liu

    (Chinese Academy of Sciences)

  • Zheng-Jiang Zhu

    (Chinese Academy of Sciences)

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.

Suggested Citation

  • Xinyu Mei & Yuan Guo & Zhangdan Xie & Yedan Zhong & Xiaofen Wu & Daichao Xu & Ying Li & Nan Liu & Zheng-Jiang Zhu, 2021. "RIPK1 regulates starvation resistance by modulating aspartate catabolism," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26423-4
    DOI: 10.1038/s41467-021-26423-4
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