# Platelet mitochondrial function in health and disease

> **NIH NIH R01** · YALE UNIVERSITY · 2022 · $505,822

## Abstract

PROJECT SUMMARY/ABSTRACT
With the increasing prevalence of obesity in the USA, diabetes mellitus is a growing concern. Most diabetic
patients will die from a thrombotic vascular event (heart attack or stroke) where the effects of oxidative
stress on platelets, arising from major metabolic disturbances such has hyperglycemia, play a major role.
How oxidative stress directly leads to platelet dysfunction is currently an intense area of investigation. We
have recently performed rigorous proteomic and metabolomic profiling in diabetic versus healthy platelets
and identified specific oxidized methionine modifications in key mitochondrial metabolic proteins, that may
be the source for some of the major cellular metabolic disturbances (defects in mitophagy and lipid beta-
oxidation) associated with diabetic platelets. Moreover, MsrB2, an understudied mitochondrial matrix
enzyme, can reverse these oxidative-stress induced methionine oxidative changes, protecting platelets.
Based upon our Preliminary Studies we hypothesize that DM associated oxidative stress modifies key
proteins involved in essential cellular biological and biochemical processes; mitochondria specific MsrB2
may play a critical role in reversing such potentially harmful changes, thus protecting DM patients from
thrombovascular events. In addressing our hypothesis, we present three Specific Aims. Specific Aim #1 will
be to assess the effects of oxidative stress on Parkin and the recently described platelet mitophagy
protective process. Specific Aim #2 will be to determine whether methionine modification of HADHA, a key
component of the mitochondrial trifunctional protein, perturbs mitochondrial beta-oxidation. The third
Specific Aim addresses whether MsrB2 plays a role in rectifying these disturbances, in addition to possible
other anti-oxidant avenues for therapy. Our team of internationally recognized experts in the areas of
diabetes mellitus, platelet biology, mitochondrial biology and metabolism, will in the short term decipher
important new mechanisms regulating mitochondrial dysfunction and apoptosis in diabetes mellitus. In the
long term, we will have identified new targets for novel therapy against platelet mediated adverse
cardiovascular events in diabetes mellitus.

## Key facts

- **NIH application ID:** 10390280
- **Project number:** 5R01HL122815-07
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** JOHN HWA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $505,822
- **Award type:** 5
- **Project period:** 2015-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10390280

## Citation

> US National Institutes of Health, RePORTER application 10390280, Platelet mitochondrial function in health and disease (5R01HL122815-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10390280. Licensed CC0.

---

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