Bnip3/Nix-mediated mitophagy protects memory B cells by restricting de novo fatty acid synthesis
| Autor: | Srikanth Kodali |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 204:155.7-155.7 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Immunological memory preserved by long-lived memory cells forms the basis for long-term protection by the adaptive immune system against repeat infections. Autophagy is crucial for the longevity of memory cells, though the molecular mechanisms for this phenomenon remain unclear. Bnip3 and its homolog Nix are Bcl-2 family proteins that localize to the outer mitochondrial membrane. Here, we show that autophagic clearance of mitochondria mediated by Bnip3 and Nix is critical to maintain mitochondrial homeostasis and prolong memory B cell survival. In mice with deletion of Nix and Bnip3 in B cells, memory B cells formed normally, but declined in numbers thereafter. Nix- and Bnip3-deficient memory B cells had impaired mitophagy and accumulated both total and functional mitochondria. Interestingly, Nix- and Bnip3-deficient memory B cells also had increased lipid droplets and elevated expression of genes required for de novo fatty acid synthesis. Inhibition of the fatty acid synthesis enzyme acetyl-CoA carboxylase 1 (ACC1) prevented lipid accumulation and rescued Nix- and Bnip3-deficient memory B cell numbers in vivo. Our results suggest that Nix and Bnip3 mediate the autophagy of excess functional mitochondria in memory B cells to limit de novo fatty acid synthesis and protect against steatosis-related cell death. |
| Databáze: | OpenAIRE |
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