# Role of Mitochondrial c-Src in Right Ventricular Dysfunction in Pulmonary Hypertension

> **NIH NIH R01** · OCEAN STATE RESEARCH INSTITUTE, INC. · 2024 · $435,362

## Abstract

Project Summary/Abstract
Pulmonary hypertension (PH) is associated with poor prognosis. Right ventricular (RV) dysfunction/failure
consequent to high RV afterload is the primary cause of morbidity and mortality in PH, yet no RV targeted
therapies are available. This contrasts with several drug classes that are beneficial in LV dysfunction. Therefore,
there remains an unmet need to therapeutically target the mechanisms underlying RV dysfunction to improve
long-term outcomes in PH. Cardiomyocytes determine RV function in PH. Mitochondria through oxidative
phosphorylation (OXPHOS) are the major source of energy in the heart. Targeting RV mitochondrial
bioenergetics and function in settings of PH may provide novel therapeutic strategies to improve RV function in
PH. Respiratory complexes in the mitochondrial electron transport chain play a critical role in oxidative
phosphorylation (OXPHOS) and generation of reactive oxygen species. OXPHOS machinery subunits have
been found to be highly phosphorylated, implicating phosphorylation as a means whereby OXPHOS is regulated.
To date, tyrosine phosphorylation (P-Tyr) is recognized as a critical regulatory mechanism in mitochondria and
c-Src is the major tyrosine kinase localized in mitochondria. The overall goal of this proposal is to delineate the
mechanisms underlying impaired RV mitochondrial energetics and function in PH. Our preliminary findings
strongly support a novel mechanism governing RV complex I assembly and function in PH that is mediated by
P-Tyr of complex proteins. Completion of this study is expected to identify a new targeted strategy to
preserve/restore electron transfer chain function in RV cardiomyocytes in vivo in settings of PH.

## Key facts

- **NIH application ID:** 10883063
- **Project number:** 1R01HL169456-01A1
- **Recipient organization:** OCEAN STATE RESEARCH INSTITUTE, INC.
- **Principal Investigator:** Gaurav Choudhary
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $435,362
- **Award type:** 1
- **Project period:** 2024-05-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10883063

## Citation

> US National Institutes of Health, RePORTER application 10883063, Role of Mitochondrial c-Src in Right Ventricular Dysfunction in Pulmonary Hypertension (1R01HL169456-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10883063. Licensed CC0.

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