Regulation of intracellular heme trafficking revealed by subcellular reporters

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Abstract
Significance: The intracellular and extracellular trafficking of heme, a hydrophobic and potentially cytotoxic cofactor in proteins such as hemoglobin, remains an underexplored area. While cellular heme can be derived exogenously or from de novo synthesis, it is unclear if there is differential trafficking of heme from these two sources. To critically examine this possibility, we developed peroxidase-based enzymatic reporters for heme and deployed them in subcellular compartments in mammalian cells and in several tissues in theCaenorhabditiselegansanimal model. Our results show that extracellular and endogenous heme is trafficked to virtually all intracellular compartments via distinct cellular routes and that interorgan heme transport is essential for systemic regulation of heme homeostasis inC. elegans.
Funding Information
  • HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (DK074797)
  • HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (DK090257)
  • HHS | NIH | National Institute of Environmental Health Sciences (ES025661)
  • National Science Foundation (MCB1552791)

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