Pearson syndrome-like anemia induced by accumulation of mutant mtDNA and anemia with imbalanced white blood cell lineages induced by Drp1 deletion in a murine model

Pharmacol Res. 2022 Nov:185:106467. doi: 10.1016/j.phrs.2022.106467. Epub 2022 Sep 28.


Regulation of mitochondrial respiration and morphology is important for maintaining steady-state hematopoiesis, yet few studies have comparatively evaluated the effects of abnormal mitochondrial respiration and dynamics on blood-cell differentiation in isolation or combination. This study sought to explore these effects in mouse models with one or both of the following deficits: a large-scale deletion of mitochondrial DNA (ΔmtDNA), accumulated to varying extents, or knockout of the mitochondrial fission factor Drp1. Each deficit was found to independently provoke anemia but with clearly different manifestations. The former showed signs of aberrant respiration, analogous to Pearson syndrome, while the latter showed signs of abnormal mitochondrial dynamics and was associated with changes in the relative proportions of leukocyte lineages. Combining these deficits acted to amplify abnormal iron metabolism in erythropoiesis, exacerbating anemia in an additive manner. Our results indicate that mitochondrial respiration and dynamics play distinct roles in different sets of processes and cell lineages in hematopoietic differentiation.

Keywords: Anemia; Drp1; Mitochondria; Pearson syndrome; ΔmtDNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia* / genetics
  • Animals
  • DNA, Mitochondrial* / genetics
  • Disease Models, Animal
  • Leukocytes
  • Mice


  • DNA, Mitochondrial

Supplementary concepts

  • VLCAD deficiency