@entity183 deficient erythroid cells up-regulate XXXX and down-regulate mitochondrial biogenesis and metabolism.

@entity1 @entity16344 @entity417 @entity14713 @entity19 @entity2974 @entity72492 @entity5985 @entity855 @entity5714 @entity183 @entity236 @entity224 @entity3654 @entity599 @entity68
BACKGROUND: @entity19 irradiated and reconstituted with hematopoietic cells lacking manganese @entity224 dismutase ( @entity183 ) show a persistent @entity5714 similar to @entity1 @entity417 ( @entity417 ), including characteristic intra-mitochondrial @entity68 deposition. @entity417 is primarily an acquired, @entity236 occurring in individuals over 60 years of age with uncertain etiology. METHODOLOGY/PRINCIPAL FINDINGS: To define early events in the pathogenesis of this @entity19 model of @entity417 , we compared erythroid differentiation of @entity183   /    and normal bone marrow cells using flow cytometry and gene expression profiling of erythroblasts. The predominant transcriptional differences observed include widespread down-regulation of mitochondrial metabolic pathways and mitochondrial biogenesis. Multiple nuclear encoded subunits of complexes I-IV of the electron transport chain, @entity855 synthase (complex V), @entity2974 cycle and mitochondrial ribosomal proteins were coordinately down-regulated in @entity183   /    erythroblasts. Despite @entity68 accumulation within mitochondria, we found increased expression of @entity3654 receptor, @entity16344 , at both the transcript and protein level in @entity183 deficient cells, suggesting deregulation of @entity68 delivery. Interestingly, there was decreased expression of @entity72492 , the gene responsible for @entity14713 , a component required for @entity5985 cluster biogenesis. CONCLUSIONS/SIGNIFICANCE: These results indicate that in erythroblasts, mitochondrial oxidative stress reduces expression of multiple nuclear genes encoding components of the respiratory chain, @entity2974 cycle and mitochondrial protein synthesis. An additional target of particular relevance for @entity417 is @entity68 : @entity599 cluster biosynthesis. By decreasing transcription of components of cluster synthesis machinery, both @entity68 utilization and regulation of @entity68 uptake are impacted, contributing to the sideroblastic phenotype.
