# Importance and Regulation of Cardiac Mitochondrial Pyruvate Transport

> **NIH NIH R00** · SAINT LOUIS UNIVERSITY · 2021 · $249,000

## Abstract

Abstract
In this K99/R00 Pathway to Independence award application, Dr. Kyle McCommis outlines detailed plans to
enhance his research training in state-of-the-art cardiovascular metabolism techniques while simultaneously
addressing a novel mechanism to altered metabolism during various cardiomyopathies. Dr. McCommis is
currently a postdoctoral research scholar at the Washington University School of Medicine, and has a strong
background in assessing cardiac function, and the role of mitochondria in cardioprotection. Kyle’s recent
research training delved into hepatic and β-cell mitochondrial pyruvate metabolism. Herein, he seeks to marry
these two areas of research expertise to investigate the importance of mitochondrial pyruvate metabolism in
the heart. A primary goal of Dr. McCommis is to become an independent investigator in cardiometabolic
research, thus a career development plan has been proposed in which he will train with experts in various
aspects of cardiac metabolism (Drs. Finck, Lewandowski, and Schaffer). From Dr. Lewandowski he will learn:
(1) the isolated perfused mouse heart preparation, (2) expand upon Kyle’s experience using tracers to
understand metabolic pathways, and (3) NMR analysis of tracer metabolite flux. From Drs. Finck and Schaffer,
Kyle will learn: (1) the molecular and cellular alterations that occur in diabetic hearts, (2) the nuances of
running a research laboratory, and (3) guidance on initiating and developing an independent research career.
Collaborators have also been identified to instruct Kyle on the isolation of primary adult cardiomyocytes as well
as provide assistance with performing and interpreting metabolomic analyses.
Metabolism of pyruvate is essential for the working heart which requires large amounts of ATP to fuel
contraction. During cardiac ischemia, hypertrophy, or diabetes, pyruvate metabolism is significantly diminished.
However, the mechanisms of these metabolic alterations are far from understood. Regulation of the activity of
the newly identified mitochondrial pyruvate carrier (MPC) likely plays a role in these adaptations. However,
nothing is known regarding the regulation of the MPC in the heart or how pathogenic conditions associated
with impaired pyruvate utilization affects MPC activity. The goals of this work are to: (1) determine the
acetylation status and activity of the MPC complex during ischemia, hypertrophy, and diabetic cardiomyopathy,
(2) identify the deacetylase responsible for modifying MPC proteins, (3) identify the acetylated lysine residue(s)
of MPC2, (4) phenotypically characterize the cardiac function and metabolism of cardiac-specific MPC2-null
(CS-MPC2-/-) mice, and (5) analyze the response of CS-MPC2-/- mice to diabetes, hypertrophy, and ischemia.
The overarching goal of this proposal is to develop Dr. McCommis into a productive independent investigator.
The knowledge and experience obtained from the proposed research and career development plans will
provide him the bo...

## Key facts

- **NIH application ID:** 10152377
- **Project number:** 5R00HL136658-05
- **Recipient organization:** SAINT LOUIS UNIVERSITY
- **Principal Investigator:** Kyle S McCommis
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2019-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10152377

## Citation

> US National Institutes of Health, RePORTER application 10152377, Importance and Regulation of Cardiac Mitochondrial Pyruvate Transport (5R00HL136658-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10152377. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*