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Pathogenic mitochondrial DNA‐induced respiration defects in hematopoietic cells result in anemia by suppressing erythroid differentiation
Author(s) -
Inoue Shin-Ichi,
Yokota Mutsumi,
Nakada Kazuto,
Miyoshi Hiroyuki,
Hayashi Jun-Ichi
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.03.092
Subject(s) - haematopoiesis , mitochondrial dna , microbiology and biotechnology , respiration , mitochondrion , dna , biology , anemia , chemistry , genetics , medicine , stem cell , gene , anatomy
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 (ΔmtDNA) into normal mice. The bone marrow‐transplanted mice carried high proportion of ΔmtDNA 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.