# Mechanisms of Mitochondrial Ultrastructural Changes and Metabolic Dysfunction Caused by Calcium Overload

> **NIH NIH F31** · MICHIGAN STATE UNIVERSITY · 2020 · $34,740

## Abstract

Project Summary/Abstract:
Myocardial ischemia/reperfusion (IR) is an injury preceded by mitochondrial dysfunction caused by calcium
overload. While mitochondrial calcium dynamics and molecular pathways have been extensively studied, little
is known on how mitochondria accumulate and store calcium and how calcium overload effects mitochondrial
function. This is significant since the main cause of cardiac tissue and cell death after a myocardial infarction is
mediated by mitochondrial calcium overload. As there are no adequate treatments available, the nature of
calcium storage and its impact on mitochondrial function requires further study. Herein, we show preliminary
results that reveal an unprecedented link between cristae structure and mitochondrial function during calcium
overload. The presented data suggest that preserving cristae during calcium overload confer protection against
calcium overload. Confirming this hypothesis will add an exciting new therapeutic approach and puts in
immediate play proteins not considered as drug targets to treat IR injury. The objectives of this proposal
are 1) to characterize and quantify the calcium sequestration system and the direct effects on mitochondrial
function, 2) to determine the functional impact of cristae remodeling in mitochondria ultrastructure associated
with calcium overload, and 3) establish how known modulators of the calcium sequestration system alter
mitochondrial function. The experimental approach in this proposal will use recent methods of advanced cryo-
EM, spectrofluorimetry, ex vivo heart perfusion system, and high-resolution respirometry. Bioenergetic and
functional data will be measured from isolated cardiac mitochondria from healthy, ischemic, and IR injured
guinea pig hearts. In addition, support from this fellowship will be directed to acquire experimental and
academic skills sets that are key to the proposal success. These will be approached by taking high-quality
courses offered at MSU, hands-on training, workshops, and regional and national conferences. Gathering
scientific expertise via the F31 Award in mitochondria and cellular physiology will provide opportunities for
improving scientific communication through talks, posters, and manuscript writing. The opportunity granted via
the F31 Award will continue and expand this work to encompass the bioenergetic consequences between
mitochondrial calcium overload and mitochondrial ultrastructure related to a pathophysiological scenario such
as IR injury. The combined efforts of the fellowship award, extensive expertise of sponsors, co-sponsors,
collaborator, and the institution’s commitment to excellence is an optimal pathway to independence that will
help unlock the potential as a successful scientist.

## Key facts

- **NIH application ID:** 9991236
- **Project number:** 1F31HL152623-01
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Jasiel Omil Strubbe
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $34,740
- **Award type:** 1
- **Project period:** 2020-05-16 → 2023-05-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991236

## Citation

> US National Institutes of Health, RePORTER application 9991236, Mechanisms of Mitochondrial Ultrastructural Changes and Metabolic Dysfunction Caused by Calcium Overload (1F31HL152623-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9991236. Licensed CC0.

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