Free fatty-acid transport via CD36 drives β-oxidation-mediated hematopoietic stem cell response to infection

Jayna J. Mistry; Charlotte Hellmich; Jamie A. Moore; Aisha Jibril; Iain Macaulay; Mar Moreno-Gonzalez; Federica Di Palma; Naiara Beraza; Kristian M. Bowles; Stuart A. Rushworth

doi:10.1038/s41467-021-27460-9

Free fatty-acid transport via CD36 drives β-oxidation-mediated hematopoietic stem cell response to infection

Jayna J. Mistry, Charlotte Hellmich, Jamie A. Moore, Aisha Jibril, Iain Macaulay, Mar Moreno-Gonzalez, Federica Di Palma, Naiara Beraza, Kristian M. Bowles, Stuart A. Rushworth

Research output: Contribution to journal › Article › peer-review

51 Citations (Scopus)

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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.

Original language	English
Article number	7130
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-27460-9
Publication status	Published - 8 Dec 2021

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10.1038/s41467-021-27460-9Licence: CC BY

Published_VersionFinal published version, 1.71 MBLicence: CC BY

https://www.nature.com/articles/s41467-021-27460-9Licence: CC BY

Investigation of mitochondrial fate in normal and malignant haematopoiesis.
Rushworth, S., Bowles, K., Croft, A. & Croft, A.
Medical Research Council
1/03/21 → 31/08/24
Project: Research

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@article{0d28eed685d34293b5e00224333a2326,

title = "Free fatty-acid transport via CD36 drives β-oxidation-mediated hematopoietic stem cell response to infection",

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.",

author = "Mistry, {Jayna J.} and Charlotte Hellmich and Moore, {Jamie A.} and Aisha Jibril and Iain Macaulay and Mar Moreno-Gonzalez and {Di Palma}, Federica and Naiara Beraza and Bowles, {Kristian M.} and Rushworth, {Stuart A.}",

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doi = "10.1038/s41467-021-27460-9",

language = "English",

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journal = "Nature Communications",

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Free fatty-acid transport via CD36 drives β-oxidation-mediated hematopoietic stem cell response to infection. / 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.

In: Nature Communications, Vol. 12, No. 1, 7130 , 08.12.2021.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Free fatty-acid transport via CD36 drives β-oxidation-mediated hematopoietic stem cell response to infection

AU - Mistry, Jayna J.

AU - Hellmich, Charlotte

AU - Moore, Jamie A.

AU - Jibril, Aisha

AU - Macaulay, Iain

AU - Moreno-Gonzalez, Mar

AU - Di Palma, Federica

AU - Beraza, Naiara

AU - Bowles, Kristian M.

AU - Rushworth, Stuart A.

PY - 2021/12/8

Y1 - 2021/12/8

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-021-27460-9

DO - 10.1038/s41467-021-27460-9

M3 - Article

VL - 12

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 7130

ER -

Free fatty-acid transport via CD36 drives β-oxidation-mediated hematopoietic stem cell response to infection

Abstract

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Projects

Investigation of mitochondrial fate in normal and malignant haematopoiesis.

Cite this