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Glutamine gluttony of efferocytes

Nature Metabolism volume 3, pages 1280–1281 (2021)Cite this article

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Dysfunctional efferocytosis impairs clearance of apoptotic cells in disease. A new study shows that glutamine catabolism supports efficient apoptotic cell efferocytosis via non-canonical glutamine transamination but not canonical GLUD1-dependent α-ketoglutarate production, in a process that may operate in human atherosclerosis.

Efferocytosis is known to rely on aerobic glycolysis during engulfment of ACs, indicated by increased glucose uptake and enhanced lactate release2, but also requires mitochondrial metabolism to degrade accumulating long-chain fatty acids via fatty acid oxidation (FAO)3. Moreover, mitochondrial uncoupling protein 2 (UCP2) enhances efferocytosis by lowering the mitochondrial membrane potential in phagocytes4. Finally, arginine and ornithine derived from ACs are metabolized into the polyamine putrescine pathway in macrophages via arginase 1 and ornithine decarboxylase to enable actin cytoskeletal rearrangements during efferocytosis5. Glutamine, on the other hand, is crucial for supporting alternative (M2-like) macrophage polarization and anti-inflammatory phenotype in macrophages6,7. Glutaminolysis consists of glutamine hydrolyzation into glutamate by GLS1, and this metabolic process is known to be upregulated in IL4-induced reparative macrophages. However, whether glutamine catabolism can bridge the anti-inflammatory response through the machinery of efferocytosis had remained unknown up until now.

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Fig. 1: Reparative macrophages bypass the canonical glutamine metabolism pathway to potentiate efferocytosis.

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Author notes

  1. These authors contributed equally: Alison Jaccard, Xiaoyun Li.

Authors and Affiliations

  1. Department of Fundamental Oncology, University of Lausanne, Lausanne, Switzerland

    Alison Jaccard, Xiaoyun Li & Ping-Chih Ho

  2. Ludwig Institute for Cancer Research, University of Lausanne, Epalinges, Switzerland

    Alison Jaccard, Xiaoyun Li & Ping-Chih Ho

Authors
  1. Alison Jaccard
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  2. Xiaoyun Li
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  3. Ping-Chih Ho
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Corresponding authors

Correspondence to Alison Jaccard or Ping-Chih Ho.

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The authors declare no competing interests.

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Jaccard, A., Li, X. & Ho, PC. Glutamine gluttony of efferocytes. Nat Metab 3, 1280–1281 (2021). https://doi.org/10.1038/s42255-021-00462-z

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