Regulation of mitochondrial biogenesis in erythropoiesis by mTORC1-mediated protein translation
Abstract
Advances in genomic profiling present new challenges of explaining how changes in DNA and RNA are translated into proteins linking genotype to phenotype. Here we compare the genome-scale proteomic and transcriptomic changes in human primary haematopoietic stem/progenitor cells and erythroid progenitors, and uncover pathways related to mitochondrial biogenesis enhanced through post-transcriptional regulation. Mitochondrial factors including TFAM and PHB2 are selectively regulated through protein translation during erythroid specification. Depletion of TFAM in erythroid cells alters intracellular metabolism, leading to elevated histone acetylation, deregulated gene expression, and defective mitochondria and erythropoiesis. Mechanistically, mTORC1 signalling is enhanced to promote translation of mitochondria-associated transcripts through TOP-like motifs. Genetic and pharmacological perturbation of mitochondria or mTORC1 specifically impairs erythropoiesis in vitro and in vivo. Our studies support a mechanism for post-transcriptional control of erythroid mitochondria and may have direct relevance to haematologic defects associated with mitochondrial diseases and ageing.
Associated Datasets
References
Citations
Mitochondrial acetyl-CoA reversibly regulates locus-specific histone acetylation and gene expression
Datasets Mentioned
Methods Mentioned
Software Mentioned
Related Concepts
Related Feeds
Cell Aging
This feed focuses on cellular aging with emphasis on mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.
Aging Genetics (Keystone)
This feed focuses on aging epidemiology and genetic, epigenetic, and proteomic aspects underlying aging, as well as aging- associated biomarkers. Here the latest research in this domain.
Aging-Associated Metabolic Disorders
Age is associated with many metabolic disorders including cardiovascular diseases, type 2 diabetes, stroke and heart disease. The mediators in aging process have been suggested to play a part in the cellular processes responsible for these metabolic disorders. Here is the latest research on aging-associated metabolic disorders.
Cancer Epigenetics & Metabolism (Keystone)
Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.
Genetics & Epigenetics of Aging
Dozens of genes are implicated in lifespan, and epigenetic changes during aging affect cell function. This feed focuses on the genetics and epigenetics of aging.
Cell Aging (Keystone)
This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.