# Mitochondrial Fatty Acid Synthesis and the Coordinate Regulation of Respiration

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $293,563

## Abstract

Project Summary
The proposed project is a renewal of a previously funded project that was focused on the
discovery and characterization of assembly factors for the mitochondrial respiratory
complexes. During these studies, we made the unexpected observation that the
assembly and activation of those complexes is strictly dependent upon the rather poorly
understood mitochondrial fatty acid synthesis (mtFAS) pathway. When this pathway is
active, it synthesizes acyl chains that are covalently attached to the Acp1 scaffold
protein, which when acylated binds and activates the LYR family of regulators that are
required for respiratory complex assembly and iron-sulfur cluster biogenesis. We further
demonstrated that the activity of mtFAS and the acylation state of Acp1 is sensitive to
the availability of mitochondrial acetyl-coA, which is also the principal fuel for
mitochondrial oxidative metabolism. Therefore, we hypothesize that this system provides
an elegant mechanism to enable the coupling of assembly and activation of the
mitochondrial respiratory system with the availability of substrates for that system. To
test this hypothesis and better define the underlying mechanisms, we propose the follow
aims. Aim 1) Define the role of mtFAS in the regulation of iron-sulfur cluster
synthesis. Aim 2) Define the mtFAS and LYR-dependent regulation of OXPHOS
biogenesis. Aim 3) Discover and characterize novel targets of mtFAS and ACP
regulation. We propose that a better understanding of mtFAS and how it regulates
activation of Acp1 targets could lead to therapeutic approaches to boost and optimize
mitochondrial respiration.

## Key facts

- **NIH application ID:** 10000162
- **Project number:** 5R01GM110755-07
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Dennis R. Winge
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $293,563
- **Award type:** 5
- **Project period:** 2014-05-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000162

## Citation

> US National Institutes of Health, RePORTER application 10000162, Mitochondrial Fatty Acid Synthesis and the Coordinate Regulation of Respiration (5R01GM110755-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10000162. Licensed CC0.

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