# Mitophagy as a regulator of cardiac function in physiological and pathophysiological conditions

> **NIH NIH K22** · OHIO STATE UNIVERSITY · 2020 · $242,690

## Abstract

7. Project Summary
 Mitochondria provide an essential source of energy and play an important role during cardiac development
and in heart failure progression. Cumulative evidence illustrates the importance of mitochondrial quality control
in cardiac function during fetal life and in the adult heart. This K22 application centers on a research proposal
to study the role of cardiac mitophagy, an important aspect of mitochondrial quality control, in both
physiological and pathophysiological conditions within the context of a career development program. The
program is designed to facilitate a successful transition from postdoctoral training to independent research.
These studies will be facilitated by my recently described mt-Keima mouse model to monitor in vivo cardiac
mitophagic flux, as well as the use of genetic Parkin deficient (a positive mitophagy regulator) and USP30
deficient (a negative mitophagy regulator) mouse models. This will be supplemented by detailed cardiac
functional analysis using murine models of transverse aortic constriction induced cardiomyopathy. In particular,
I will determine the role of mitophagy in perinatal cardiac mitochondrial maturation and during cardiac
pathological stresses, as well as test a specific USP30 inhibitor in stimulating cardiac mitophagy and in
attenuating progression of heart failure (Aim 1). It is increasingly recognized that mitophagy is critical for
mitochondrial plasticity and metabolic reprogramming during normal heart development and in various disease
conditions. I will further test the hypothesis that the rate limiting enzyme in fatty acid oxidation, CPT1a, may
regulate mitophagy. Using a cardiac specific CPT1a knockout mouse, I will assess whether CPT1a regulates
the mitochondrial perinatal metabolic transition and the adult mitophagic response that occurs following cardiac
stress (Aim 2). Completion of the proposed Research Strategy will produce critical insights into the role of
mitophagy in normal cardiovascular physiology and pathological conditions, and will fundamentally advance
our understanding of the interaction between mitochondrial metabolism and mitochondrial quality control in the
heart. This enhanced understanding of the role of mitophagy, USP30 and CPT1a in the heart should open
possibilities for harnessing these pathways for therapeutic potential. These studies will be initiated within the
NIH intramural program and completed during an extramural, independent phase.
 Through this K22 Career Development Award proposal, I seek to systematically acquire additional
mentored research training and career development training at the NIH/NHLBI through a detailed Career
Development Plan designed to complement my current skill set, including additional formal training in cardiac
physiology and pathophysiology. With the continued support of members of my Advisory Committee, the K22
Career Development Award will establish a training framework to initiate the research program in preparation...

## Key facts

- **NIH application ID:** 9984839
- **Project number:** 5K22HL135051-03
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Nuo Sun
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $242,690
- **Award type:** 5
- **Project period:** 2018-08-15 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984839

## Citation

> US National Institutes of Health, RePORTER application 9984839, Mitophagy as a regulator of cardiac function in physiological and pathophysiological conditions (5K22HL135051-03). Retrieved via AI Analytics 2026-07-24 from https://api.ai-analytics.org/grant/nih/9984839. Licensed CC0.

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