We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Free fatty-acid transport via CD36 drives β-oxidation-mediated hematopoietic stem cell response to infection.
- Authors
Mistry, Jayna J.; Hellmich, Charlotte; Moore, Jamie A.; Jibril, Aisha; Macaulay, Iain; Moreno-Gonzalez, Mar; Di Palma, Federica; Beraza, Naiara; Bowles, Kristian M.; Rushworth, Stuart A.
- Abstract
Acute infection is known to induce rapid expansion of hematopoietic stem cells (HSCs), but the mechanisms supporting this expansion remain incomplete. Using mouse models, we show that inducible CD36 is required for free fatty acid uptake by HSCs during acute infection, allowing the metabolic transition from glycolysis towards β-oxidation. Mechanistically, high CD36 levels promote FFA uptake, which enables CPT1A to transport fatty acyl chains from the cytosol into the mitochondria. Without CD36-mediated FFA uptake, the HSCs are unable to enter the cell cycle, subsequently enhancing mortality in response to bacterial infection. These findings enhance our understanding of HSC metabolism in the bone marrow microenvironment, which supports the expansion of HSCs during pathogenic challenge. Hematopoietic stem cells (HSCs) rapidly expand upon infection, switching their metabolic profile to increase OXPHOS. Here, the authors show in mouse models that infection promotes uptake of long-chain free fatty acids via CD36, which is required for a protective response.
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-27460-9