# mitoAMPK in exercise benefits

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2021 · $425,872

## Abstract

PROJECT SUMMARY/ABSTRACT
 Regular exercise promotes physical performance and health, and prevent various types of diseases. These
benefits are largely mediated by responses and adaptations, particularly mitochondrial remodeling, in skeletal
muscle. 5' AMP-activated protein kinase (AMPK) is a bioenergetics sensor that is critical for the maintenance
of metabolic homoeostasis, and AMPK signaling has been linked to mitochondrial remodeling and functional
adaptations under normal and disease conditions. However, the precise mechanism of AMPK signaling in
control of mitochondrial remodeling with subcellular specificity remains obscure. We discovered a physical
association of a novel AMPK complex (α1, β2 and γ1 subunits) with mitochondria (referred to as mitoAMPK) in
and unveiled its activation (T172 phosphorylation) under exercise and ischemic conditions. We have also
obtained preliminary data to show that inhibition of mitoAMPK blocks exercise-induced mitophagy, a key step
in mitochondrial quality control, in skeletal muscle. We now propose a completely novel hypothesis that
mitoAMPK is preferentially activated at energetically stressed mitochondria during exercise, mediating
precision mitophagy of dysfunctional or damaged mitochondria for functional and metabolic
adaptations To test this hypothesis, we propose:
1) Determine if mitoAMPK is preferentially activated at energetically stressed mitochondria in skeletal muscle.
2) Elucidate the role of mitoAMPK in exercise-induced mitophagy.
3) Eetermine the functional role of mitoAMPK in exercise training-induced functional and metabolic
adaptations.
 The proposed studies will capitalize on our novel findings of mitoAMPK that reveals completely new
regulatory and functional features of this important signaling molecule in muscle biology and metabolism. The
experimental design and model systems are both conceptually and technically innovative. The findings will
significantly improve the mechanistic understanding of exercise-induced mitophagy and adaptations, with great
potential impact on the future development of therapeutics for treatment and prevention ofchronic diseases,
like type 2 diabetes.

## Key facts

- **NIH application ID:** 10172852
- **Project number:** 5R01AR077440-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Zhen Yan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $425,872
- **Award type:** 5
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10172852

## Citation

> US National Institutes of Health, RePORTER application 10172852, mitoAMPK in exercise benefits (5R01AR077440-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10172852. Licensed CC0.

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