# Project 5 Frascati-mediated Mitochondrial Metabolism, Barry Paw

> **NIH NIH P01** · BOSTON CHILDREN'S HOSPITAL · 2021 · $338,967

## Abstract

PROJECT SUMMARY 
The overall objective of this proposal is to identify and characterize novel proteins involved in erythroid 
iron/heme metabolism. Erythropoiesis is a massive exercise in cellular proliferation and synthesis of a single 
protein, hemoglobin. As a consequence, there is a tremendous demand for iron and heme to be efficiently 
trafficked within the developing erythron. Despite advances in our understanding of extra-cellular iron 
trafficking and proto-porphyrin biosynthesis, significant gaps remain, especially with respect to components 
involving the egress of iron from the endosomes to the mitochondria, the trafficking of iron/heme within the 
mitochondria, the transporters required for proto-porphyrin genesis, the cofactors that facilitate the intracellular 
trafficking of iron/heme, and the eventual export of heme from the mitochondria for its incorporation in 
hemoglobin. Using complementary approaches of genetics and bioinformatics from transcriptional profiling, we 
previously identified several proteins, such as Mitoferrin1 (Mfrn1), Sorting Nexin3 (Snx3), Tmem14c, Lat3, and 
Clpx1, as new components in the intracellular trafficking of iron, heme and nutrients crucial to red cell 
development. Although transcriptional profiling as provided insights, we showed that post-translational 
mechanisms play equally critical roles in the expression and function of proteins involved in iron and heme 
metabolism. Using quantitative mass spectrometry, we examined changes in the mitochondrial proteome as 
erythroid cells undergo maturation. We identified several solute carriers and transmembrane proteins, whose 
function in erythropoiesis have not been previously ascribed, that were induced with hemoglobinization. We 
propose to study the expression and loss-of-function phenotype of these 7 candidate genes (Aim 1). In 
particular, we plan to focus previously identified gene, Fam210b (c20orf108), and its interacting partners in red 
cell development (Aim 2). Functional elucidation of these structural genes will expand our knowledge into the 
unknown additional steps in intracellular solute, iron and heme trafficking crucial for erythropoiesis. The results 
of our proposal will provide us with new genetic tools to explore human disorders of anemias.

## Key facts

- **NIH application ID:** 10146454
- **Project number:** 5P01HL032262-39
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Yvette Y Yien
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $338,967
- **Award type:** 5
- **Project period:** 1997-07-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146454

## Citation

> US National Institutes of Health, RePORTER application 10146454, Project 5 Frascati-mediated Mitochondrial Metabolism, Barry Paw (5P01HL032262-39). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10146454. Licensed CC0.

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