Cookies help us deliver our services. By using our services, you agree to our use of cookies. More information

Drake 2021 Proc Natl Acad Sci U S A

From Bioblast
Publications in the MiPMap
Drake JC, Wilson RJ, Laker RC, Guan Y, Spaulding HR, Nichenko AS, Shen W, Shang H, Dorn MV, Huang K, Zhang M, Bandara AB, Brisendine MH, Kashatus JA, Sharma PR, Young A, Gautam J, Cao R, Wallrabe H, Chang PA, Wong M, Desjardins EM, Hawley SA, Christ GJ, Kashatus DF, Miller CL, Wolf MJ, Periasamy A, Steinberg GR, Hardie DG, Yan Z (2021) Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy. Proc Natl Acad Sci U S A 118:e2025932118.

» PMID: 34493662 Open Access

Drake Joshua C, Wilson Rebecca J, Laker Rhianna C, Guan Yuntian, Spaulding Hannah R, Nichenko Anna S, Shen Wenqing, Shang Huayu, Dorn Maya V, Huang Kian, Zhang Mei, Bandara Aloka B, Brisendine Matthew H, Kashatus Jennifer A, Sharma Poonam R, Young Alexander, Gautam Jitendra, Cao Ruofan, Wallrabe Horst, Chang Paul A, Wong Michael, Desjardins Eric M, Hawley Simon A, Christ George J, Kashatus David F, Miller Clint L, Wolf Matthew J, Periasamy Ammasi, Steinberg Gergory R, Hardie D Grahame, Yan Zhen (2021) Proc Natl Acad Sci U S A

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. Keywords: AMPK, Exercise, Mitochondria, Mitophagy, Skeletal muscle Bioblast editor: Plangger M

Labels: MiParea: Respiration, mt-Biogenesis;mt-density, mt-Structure;fission;fusion, mt-Membrane 

Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS  HRR: Oxygraph-2k