AK2 deficiency compromises the mitochondrial energy metabolism required for differentiation of human neutrophil and lymphoid lineages

• DOI: 10.1038/cddis.2015.211
• Publication Date: 2015-08-13T15:48:47Z
• Authors: E Six; C Lagresle-Peyrou; S Susini; C De Chappedelaine; N Sigrist; H Sadek; M Chouteau; N Cagnard; M Fontenay; O Hermine; C Chomienne; P Reynier; A Fischer; I André-Schmutz; N Gueguen; M Cavazzana
• Keywords: 0301 basic medicine; Neutrophils; Primary Cell Culture; Antigens, CD34; HL-60 Cells; Oxidative Phosphorylation; adenylate kinase; 03 medical and health sciences; Humans; Lymphocytes; Antigens; Adenine Nucleotides; Gene Expression Profiling; Stem Cells; Adenylate Kinase; Cell Differentiation; Leukopenia; Mitochondria; 3. Good health; mitochondria; Gene Expression Regulation; Gene Knockdown Techniques; Mutation; Original Article; Severe Combined Immunodeficiency; CD34; [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology

Abstract Reticular dysgenesis is a human severe combined immunodeficiency that primarily characterized by profound neutropenia and lymphopenia. The condition caused mutations in the adenylate kinase 2 (AK2) gene, resulting loss of mitochondrial AK2 protein expression. regulates homeostasis adenine nucleotides (ADP, ATP AMP) catalyzing transfer high-energy phosphate. Our present results demonstrate AK2-knocked-down progenitor cells have poor proliferative survival capacities are blocked their differentiation toward lymphoid granulocyte lineages. We also observed deficiency impaired function general oxidative phosphorylation particular – showing critical control energy metabolism. Loss disrupts this regulation leads to block myeloid cell differentiation.