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Updated: Oct 21, 2025

Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome
Published on: November 30, 2022
Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced
Joshua C Drake1,2, Rebecca J Wilson3,4, Rhianna C Laker3
1Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA 22908; zy3m@virginia.edu joshuacd@vt.edu.
Abstract:
Mitochondria form a complex, interconnected reticulum that is maintained through coordination among biogenesis, dynamic fission, and fusion and mitophagy, which are initiated in response to various cues to maintain energetic homeostasis. These cellular events, which make up mitochondrial quality control, act with remarkable spatial precision, but what governs such spatial specificity is poorly understood. Herein, we demonstrate that specific isoforms of the cellular bioenergetic sensor, 5' AMP-activated protein kinase (AMPKα1/α2/β2/γ1), are localized on the outer mitochondrial membrane, referred to as mitoAMPK, in various tissues in mice and humans. Activation of mitoAMPK varies across the reticulum in response to energetic stress, and inhibition of mitoAMPK activity attenuates exercise-induced mitophagy in skeletal muscle in vivo. Discovery of a mitochondrial pool of AMPK and its local importance for mitochondrial quality control underscores the complexity of sensing cellular energetics in vivo that has implications for targeting mitochondrial energetics for disease treatment.
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