Linking mitochondria, fatty acids and HSC expansion during infection: implications for aging and metabolic diseases

Hampton, Katherine, Polski-Delve, Alyssa, Hellmich, Charlotte and Rushworth, Stuart A. (2025) Linking mitochondria, fatty acids and HSC expansion during infection: implications for aging and metabolic diseases. Stem Cells. ISSN 1066-5099

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Abstract

In steady state, hematopoietic stem cells (HSCs) reside quiescently in their hypoxic niche with minimal mitochondrial activity, maintaining characteristically low levels of reactive oxygen species (ROS) and instead favoring glycolysis to meet their low energy requirements. However, stress, such as acute infection, triggers a state of emergency hematopoiesis during which HSCs expand more rapidly to produce up to ten-fold more downstream differentiated immune cells. To cope with this demand, HSCs increase their energy production by switching from low ATP-yielding glycolysis to high ATP-yielding mitochondrial oxidative phosphorylation. It is this metabolic switch that enables rapid HSC expansion and differentiation into downstream progeny to increase the immune cell pool and effectively clear the infection. This metabolic switch relies on the sufficient availability of healthy mitochondria as well as fuel in the form of free fatty acids to drive the necessary production of cellular components. This concise review aims to focus on how HSCs increase their mitochondrial content and fuel ATP production via fatty acid oxidation and the impact of HSC dysfunction during aging and other metabolic diseases.

Item Type:	Article
Additional Information:	Funding: K.H. and A.P.D. were supported by the UKRI BBSRC Norwich research park Bioscience doctoral training programme BB/T008717/1. C.H. was supported by the National Institute for Health and Care Research. S.A.R. was supported by the UKRI MRC project (MR/T02934X/1) and BBSRC BB/X01889X/1 (QIB/UEA partnership). Acknowledgement: Figures and graphical abstract include images from Servier Medical Art (https://smart.servier.com/), licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/)
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies
Related URLs:	https://academic.oup.com/stmcls/advance-...
Depositing User:	LivePure Connector
Date Deposited:	22 Aug 2025 15:30
Last Modified:	22 Aug 2025 15:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/100225
DOI:	10.1093/stmcls/sxaf053

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