# The heart failure interactome

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $667,019

## Abstract

Heart disease is the leading cause of death of both men and women in the US with more than
900,000 deaths each year. Heart failure is a complex disorder, characterized by impaired
myocardium contractile ability that delivers inadequate amounts of blood to meet demands of all
organs. In the heart, mitochondrial oxidative phosphorylation is the source of 90% of the
myocardial energy requirement. In the progression of heart failure, mitochondrial dysfunction
has become widely accepted as a key part of maladaptive remodeling. Changes in
mitochondrial function during heart failure have remained difficult to define on a molecular level
and include altered protein levels, conformations and protein-protein interactions. Elevation in
NADH/NAD+ ratio caused by cardiac overload was previously found to regulate mitochondrial
protein lysine acetylation and result in changes in protein interactions involving a primary
regulator of mitochondrial permeability transition pore sensitization to stress. Large-scale
quantitative interactome analysis could reveal what protein conformational and interaction
changes are involved in heart failure and provide new targets that can be tested for alleviation in
cardiac hypertrophy and dysfunction in heart failure models. This project will develop isobaric
quantitative Protein Interaction Reporter (iqPIR) technologies and apply them to study
mitochondrial protein interactions and conformational regulation in heart failure. In addition,
parallel reaction monitoring assays will be developed for iqPIR cross-linked peptides to yield a
generally useful method for quantification of protein interactions and conformational features in
any future mitochondrial study.

## Key facts

- **NIH application ID:** 10218262
- **Project number:** 5R01HL144778-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** James Edward Bruce
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $667,019
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10218262

## Citation

> US National Institutes of Health, RePORTER application 10218262, The heart failure interactome (5R01HL144778-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10218262. Licensed CC0.

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