Publications by authors named "J M Jagadeesh"
The DNA/RNA-binding Alba domain is prevalent across all kingdoms of life. First discovered in archaea, this protein domain has evolved from RNA- to DNA-binding, with a concomitant expansion in the range of cellular processes that it regulates. Despite its widespread presence, the full extent of its sequence, structural, and functional diversity remains unexplored.
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- Over 65% of body iron in mammals is found in erythrocytes, mainly as part of hemoglobin, requiring both dietary intake and recycling of iron from old blood cells.
- The SLC48A1 protein plays a crucial role in transporting heme from lysosomes to the cytoplasm, and in genetically modified mice lacking this protein, heme accumulates as hemozoin crystals in macrophages.
- These SLC48A1-deficient mice show visible hemozoin at just 8 days old, illustrating disrupted erythrocyte recycling, while studies suggest SLC48A1 is responsible for recycling a significant amount of iron equivalent to dietary levels, potentially linking human mutations of this protein to iron disorders.
Free heme is cytotoxic as exemplified by hemolytic diseases and genetic deficiencies in heme recycling and detoxifying pathways. Thus, intracellular accumulation of heme has not been observed in mammalian cells to date. Here we show that mice deficient for the heme transporter SLC48A1 (also known as HRG1) accumulate over ten-fold excess heme in reticuloendothelial macrophage lysosomes that are 10 to 100 times larger than normal.
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- Adenylate kinases (AKs) are essential enzymes that regulate energy levels in cells, with AK2 being crucial for immune system function and linked to SCID when mutated.
- In a study using zebrafish and iPSCs from an RD patient, AK2 deficiency was found to impair blood cell development, leading to energy depletion and increased cell death.
- Treating AK2-deficient zebrafish with antioxidants improved blood cell formation and suggests that antioxidant therapy could be a potential treatment for reticular dysgenesis in patients.