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Regulation of Metabolism and the Role of Redox Factors in the Energy Control of Quiescence and Proliferation of Hematopoietic Cells

  • REDOX REGULATION OF METABOLIC PROCESSES
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Abstract—One of the key regulators of hematopoietic stem cell (HSC) maintenance is cellular metabolism. Resting HSCs use anaerobic glycolysis as the main source of energy. During expansion and differentiation under conditions of steady state hematopoiesis, the energy needs of activated HSCs increase by many fold. To meet the increased demands, cells switch to mitochondrial oxidative phosphorylation, which is accompanied by an increase in reactive oxygen species (ROS) production. Here, the molecular mechanisms maintaining glycolysis in HSCs, as well as the factors determining the increase in metabolic activity and the transition to mitochondrial biogenesis during HSC activation are discussed. We focus on the role of HIF (hypoxia-inducible factor) proteins as key mediators of the cellular response to hypoxia, and also consider the phenomenon of extraphysiological oxygen shock (EPHOSS), leading to the forced differentiation of HSCs as well as methods of overcoming it. Finally, the role of fatty acid oxidation (FAO) in hematopoiesis is discussed. Understanding the metabolic needs of normal HSCs and precursors is crucial for the development of new treatments for diseases related to the hematopoietic and immune systems.

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Funding

The work was carried out within the framework of the State task of the Ministry of Science and Higher Education of the Russian Federation (state registration number of the topic—122092200053-8).

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  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russia

    M. V. Kalashnikova, N. S. Polyakova & A. V. Belyavsky

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  1. M. V. Kalashnikova
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  3. A. V. Belyavsky
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Abbreviations. ROS, reactive oxygen species; HPCs, hematopoietic progenitor cells; HSC, hematopoietic stem cells; MSCs, mesenchymal stem cells; EPHOSS, extraphysiological oxygen shock/stress; FAO (fatty acid oxidation), oxidation of fatty acids; FFA, free fatty acids; FIH, a factor that inhibits HIF; HIF, hypoxia-induced factor; OXPHOS, oxidative phosphorylation; PDK, pyruvate dehydrogenase kinase; PHD, prolyl hydroxylase.

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Kalashnikova, M.V., Polyakova, N.S. & Belyavsky, A.V. Regulation of Metabolism and the Role of Redox Factors in the Energy Control of Quiescence and Proliferation of Hematopoietic Cells. Mol Biol 57, 1165–1175 (2023). https://doi.org/10.1134/S0026893323060080

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  • DOI: https://doi.org/10.1134/S0026893323060080

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