Features of lineage-specific hematopoietic metabolism revealed by mitochondrial proteomics.

Abstract

Hematopoietic bone marrow is a regenerative tissue of high clinical relevance, yet relatively little is known about the metabolism of the stem and progenitor populations concerned. We have used a multipotent murine cell line to generate sufficient numbers of cells undergoing self-renewal, erythroid or myeloid differentiation to allow a proteomics analysis of enriched mitochondria. Stringent analysis identified 37 mitochondria-associated proteins changing on differentiation in this system. Those induced during differentiation were commonly associated with mature cell functions, while those inactivated upon differentiation indicate widespread changes in mitochondrial transport, fatty acid catabolism and oxidative phosphorylation. An erythroid specific reduction in glutamate pyruvate amino transferase 2 was confirmed at the protein level by Western blotting and at the functional level by assays of metabolite turnover. In addition to validating the dataset, these findings suggest significant differences in the core-metabolism between erythropoiesis and myelopoiesis. This knowledge is of relevance to the in vitro production of cell therapy products and to studies of the interdependence of metabolic and signaling pathways in regenerative tissues. Data are available via ProteomeXchange with identifier PXD002968.