Loss of Cpt1a results in elevated glucose-fueled mitochondrial oxidative phosphorylation and defective hematopoietic stem cells.

ABSTRACT: Hematopoietic stem cells (HSCs) rely on self-renewal to sustain stem cell potential and undergo differentiation to generate mature blood cells. Mitochondrial fatty acid β-oxidation (FAO) is essential for HSC maintenance. However, the role of carnitine palmitoyl transferase 1a (CPT1A), a key enzyme in FAO, remains unclear in HSCs. Using a Cpt1a hematopoiesis-specific conditional-KO (Cpt1aΔ/Δ) mouse model, we found that loss of Cpt1a led to HSC defects, including loss of HSC quiescence and self-renewal and increased differentiation. Mechanistically, we found that loss of Cpt1a resulted in elevated levels of mitochondrial respiratory chain complex components and their activity, as well as increased ATP production and accumulation of mitochondrial ROS in HSCs. Taken together, this suggests hyp

SUBMITTER: Li J 

PROVIDER: S-EPMC11870731 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature