title: Pathogenic mitochondrial DNA-induced respiration defects in hematopoietic cells result in anemia by suppressing erythroid differentiation.
abstract: Anemia is a symptom in patients with Pearson syndrome caused by the accumulation of mutated mitochondrial DNA (mtDNA). Such mutated mtDNAs have been detected in patients with anemia. This suggested that respiration defects due to mutated mtDNA are responsible for the anemia. However, there has been no convincing experimental evidence to confirm the pathophysiological relation between respiration defects in hematopoietic cells and expression of anemia. We address this issue by transplanting bone marrow cells carrying pathogenic mtDNA with a large-scale deletion (DeltamtDNA) into normal mice. The bone marrow-transplanted mice carried high proportion of DeltamtDNA only in hematopoietic cells, and resultant the mice suffered from macrocytic anemia. They show abnormalities of erythroid differentiation and weak erythropoietic response to a stressful condition. These observations suggest that hematopoietic cell-specific respiration defects caused by mtDNAs with pathogenic mutations are responsible for anemia by inducing abnormalities in erythropoiesis.
authors: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennohdai, Tsukuba, Ibaraki 305-8572, Japan. shinichi@brain.riken.jp <shinichi@brain.riken.jp>
authors: Shin-Ichi
authors: S
authors: Inoue
authors: Mutsumi
authors: M
authors: Yokota
authors: Kazuto
authors: K
authors: Nakada
authors: Hiroyuki
authors: H
authors: Miyoshi
authors: Jun-Ichi
authors: J
authors: Hayashi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000740:Anemia / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D019069:Cell Respiration / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D041905:Erythroid Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D028361:Mitochondrial Diseases / Q000235:genetics; D009154:Mutation
chemical_list: D004272:DNA, Mitochondrial; D045222:Electron Transport Chain Complex Proteins; D000255:Adenosine Triphosphate