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mitoAMPK in exercise benefits

mitoAMPK 在运动中的益处

基本信息

批准号：
10172852
负责人：
Zhen Yan
金额：
$ 42.59万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10172852
关键词：
5&apos -AMP-activated protein kinase Adenine Nucleotides Adult Autophagocytosis Bioenergetics Biological Models Biology CRISPR/Cas technology Chronic Disease Color Complex Cultured Cells Data Deterioration Development Diabetes Mellitus Disease Dynamin Electric Stimulation Ensure Enzymes Exercise Experimental Designs Experimental Models Fluorescence Fluorescence Resonance Energy Transfer Foundations Future Gene Transfer Health Benefit Health Promotion Heart Holoenzymes Human Image Insulin Resistance Intervention Ischemia Kidney Knockout Mice Laboratories Lead Link Maintenance Mediating Membrane Potentials Metabolic Metabolism Mitochondria Motor Mus Muscle Muscle Cells Muscle Contraction Nerve Non-Insulin-Dependent Diabetes Mellitus Nutrient Outer Mitochondrial Membrane Oxidative Phosphorylation Oxidative Stress Pharmacology Phosphorylation Phosphotransferases Physical Performance Power Plants Prevention Process Production Protein Kinase Proteins Quality Control Reactive Oxygen Species Regulation Reporter Role Running Signal Transduction Signaling Molecule Skeletal Muscle Specificity Stress Technology Testing Tissues effective intervention endurance exercise exercise capacity exercise training fight against frailty functional adaptation gain of function improved in vivo inhibitor/antagonist innovation insulin sensitivity loss of function novel physical conditioning prevent response sensor skeletal therapeutic development therapeutically effective treadmill two-photon

项目摘要

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.

项目总结/文摘