# Production of human mitochondrial ABC transporters for structural and biochemical studies

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, MERCED · 2022 · $190,320

## Abstract

Project Summary The human mitochondrial inner membrane has three ABC transporters: ABCB7 implicated
in iron transport (with mutations causing X-linked sideroblastic anemia with ataxia), ABCB8 involved in
regulation of a mitochondrial K+ channel and protection against doxorubicin toxicity, and ABCB10, which
is essential for red blood cell development, protection against oxidative stress and whose complete absence
leads to death of mice embryos. Despite their clear importance, little molecular research has been done
on these human mitochondrial transporters, mainly because production of human membrane proteins is
difficult. We believe that facilitating the production of these transporters will accelerate the research needed for
a better molecular understanding of the mechanisms underlying their function. Human ABC transporters had
only been produced in expensive and time-consuming eukaryotic systems until our group recently had the
idea of producing ABCB10 in bacteria. Our preliminary studies show that ABCB10 produced in bacteria is
functional. Here, we propose to use this novel approach for the easy, fast, and inexpensive production of
ABCB7 and ABCB8. Aim 1 will develop methodologies for expression and purification of functional ABCB7 and
ABCB8 in bacteria. Aim 2 will optimize methodologies for reconstitution of the purified transporters into a lipid
bilayer (nanodiscs and liposomes) to perform functional assays. Our proposal is of high risk because we will
test the feasibility of producing these human mitochondrial transporters in bacteria. This proposal is
significant because it will provide optimized methodologies for production and functional testing of two
important human proteins that have barely been studied, which will be of high reward. The experience of our
group on ABC transporters molecular research, combined with these new methodologies, will provide a
pathway for a more ambitious R01 proposal aimed at studying the fundamental molecular mechanisms of
these human mitochondrial transporters.

## Key facts

- **NIH application ID:** 10482375
- **Project number:** 5R21GM144810-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, MERCED
- **Principal Investigator:** Maria Elena Zoghbi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $190,320
- **Award type:** 5
- **Project period:** 2021-09-10 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10482375

## Citation

> US National Institutes of Health, RePORTER application 10482375, Production of human mitochondrial ABC transporters for structural and biochemical studies (5R21GM144810-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10482375. Licensed CC0.

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