mitoAMPK in exercise benefits
mitoAMPK in exercise benefits
批准号:
10172852
负责人:
Zhen Yan
金额:
$42.59万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
未结题
起止时间:
2020-06-01 至 2025-05-31
关键词:
5&apos-AMP-activated protein kinaseAdenine NucleotidesAdultAutophagocytosisBioenergeticsBiological ModelsBiologyCRISPR/Cas technologyChronic DiseaseColorComplexCultured CellsDataDeteriorationDevelopmentDiabetes MellitusDiseaseDynaminElectric StimulationEnsureEnzymesExerciseExperimental DesignsExperimental ModelsFluorescenceFluorescence Resonance Energy TransferFoundationsFutureGene TransferHealth BenefitHealth PromotionHeartHoloenzymesHumanImageInsulin ResistanceInterventionIschemiaKidneyKnockout MiceLaboratoriesLeadLinkMaintenanceMediatingMembrane PotentialsMetabolicMetabolismMitochondriaMotorMusMuscleMuscle CellsMuscle ContractionNerveNon-Insulin-Dependent Diabetes MellitusNutrientOuter Mitochondrial MembraneOxidative PhosphorylationOxidative StressPharmacologyPhosphorylationPhosphotransferasesPhysical PerformancePower PlantsPreventionProcessProductionProtein KinaseProteinsQuality ControlReactive Oxygen SpeciesRegulationReporterRoleRunningSignal TransductionSignaling MoleculeSkeletal MuscleSpecificityStressTechnologyTestingTissueseffective interventionendurance exerciseexercise capacityexercise trainingfight againstfrailtyfunctional adaptationgain of functionimprovedin vivoinhibitor/antagonistinnovationinsulin sensitivityloss of functionnovelphysical conditioningpreventresponsesensorskeletaltherapeutic developmenttherapeutically effectivetreadmilltwo-photon
中文摘要
项目摘要/摘要
经常锻炼有助于提高体能和身体健康,并能预防各种疾病。这些
益处在很大程度上是通过骨骼中的反应和适应,特别是线粒体重塑来实现的
肌肉。5‘AMP激活的蛋白激酶(AMPK)是一种生物能量传感器,对维持生命活动至关重要
代谢稳态,AMPK信号与线粒体重塑和功能
在正常和疾病条件下的适应。然而,AMPK信号的确切机制在
具有亚细胞特异性的线粒体重塑的控制仍然不清楚。我们发现了一个体格
一种新的AMPK复合体(α1、β2和γ1亚单位)与线粒体(称为线粒体AMPK)的关联
并揭示了其在运动和缺血条件下的激活(T172磷酸化)。我们还有
获得的初步数据表明,抑制mitoAMPK阻断运动诱导的有丝分裂是关键的一步
在线粒体质量控制中,在骨骼肌中。我们现在提出一个全新的假设
在运动过程中,线粒体在高能应激时优先激活mitoAMPK,介导
功能障碍或受损线粒体的精确有丝分裂,以实现功能和代谢
为了验证这一假设,我们建议:
1)确定mitoAMPK是否在能量应激的骨骼肌线粒体上优先激活。
2)阐明线粒体AMPK在运动诱导的线粒体吞噬中的作用。
3)确定线粒体AMPK在运动训练诱导的功能代谢中的作用
改编。
拟议的研究将利用我们对mitoAMPK的新发现,该发现揭示了全新的
这个重要的信号分子在肌肉生物学和新陈代谢中的调节和功能特征。这个
实验设计和模型系统在概念和技术上都是创新的。调查结果将
显著提高对运动诱导的有丝分裂和适应的机械理解,具有极大的
对治疗和预防慢性病的疗法未来发展的潜在影响,
比如2型糖尿病。
英文摘要
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.
期刊论文(0)
专著(0)
科研奖励(0)
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