Selective Autophagy in Normal and Malignant Hematopoiesis. Issue 1 (3rd January 2020)

• Record Type: Journal Article
• Authors: Koschade, Sebastian E.; Brandts, Christian H.
• Is Part Of: Journal of molecular biology. Volume 432:Issue 1(2020)
• Page Start: 261
• Page End: 282
• Publication Date: 2020-01-03
• Subjects: hematopoietic stem cells (HSC) -- leukemic stem cell (LSC) -- mitophagy -- leukemia -- lymphoma; HSC hematopoietic stem cell -- LSC leukemic stem cell -- MPP multipotent progenitor -- GMP granulocyte–macrophage progenitor -- NK natural killer -- ROS reactive oxygen species -- AML acute myeloid leukemia -- ALL acute lymphoblastic leukemia -- LIR LC3-interacting region -- SCID severe combined immunodeficiency -- APL acute promyelocyte leukemia -- ATRA all-trans retinoid acid -- MDS myelodysplastic syndrome -- CML chronic myeloid leukemia -- FL follicular lymphoma -- DLBCL diffuse large B-cell lymphoma -- B-NHL B-non-Hodgkin lymphoma -- EBV Epstein–Barr virus -- MCL mantle cell lymphoma -- HTLV-1 human T-cell lymphotropic virus type 1 -- CLL chronic lymphatic leukemia; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2019.06.025
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: The hierarchical organization of the hematopoietic system requires hematopoietic stem cells (HSCs) capable of self-renewal and multilineage differentiation to produce all cellular lineages of the blood. Novel techniques of purification of hematopoietic subpopulations and their functional characterization have defined individual steps of their lineage commitment. A detailed molecular map of the selective autophagy landscape governing self-renewal, maintenance, and differentiation of HSCs and their progeny during early and terminal differentiation has not yet been drawn. However, the importance of selective autophagy pathways is increasingly being recognized, as this evolutionary conserved degradation pathway is instrumental in orchestrating intracellular turnover of macromolecular complexes and organelles to meet the specific needs of various hematopoietic cells. For instance, mitophagy has clearly been demonstrated to regulate mitochondrial homeostasis in HSCs, thereby defining their metabolic fate decisions. This review focuses on the emerging evidence supporting an important role of selective autophagy in regulating normal hematopoiesis. As this has uncovered important features in malignant hematopoiesis, the review also covers aspects of selective autophagy pathways affected in the development and progression of leukemia and lymphoma. A molecular understanding of the unique requirements of selective autophagy may open new avenues for specific therapeutic intervention. Graphical Abstract: Unlabelled Image Highlights: HSCs require autophagy, particularly mitophagy, for self-maintenance under hypoxia. HSC fate decisions & differentiation are driven by mitochondrial metabolism. Autophagy defects impair lineage maturation & terminal blood cell functions. AML & other hematological malignancies require selective autophagy pathways. Details of selective autophagy pathways in hematopoiesis are still lacking.