Journal article
Ampk phosphorylation of Ulk1 is required for targeting of mitochondria to lysosomes in exercise-induced mitophagy
Nature communications, Vol.8(1), 548
09/15/2017
DOI: 10.1038/s41467-017-00520-9
PMCID: PMC5601463
PMID: 28916822
Abstract
Mitochondrial health is critical for skeletal muscle function and is improved by exercise training through both mitochondrial biogenesis and removal of damaged/dysfunctional mitochondria via mitophagy. The mechanisms underlying exercise-induced mitophagy have not been fully elucidated. Here, we show that acute treadmill running in mice causes mitochondrial oxidative stress at 3-12 h and mitophagy at 6 h post-exercise in skeletal muscle. These changes were monitored using a novel fluorescent reporter gene, pMitoTimer, that allows assessment of mitochondrial oxidative stress and mitophagy in vivo, and were preceded by increased phosphorylation of AMP activated protein kinase (Ampk) at tyrosine 172 and of unc-51 like autophagy activating kinase 1 (Ulk1) at serine 555. Using mice expressing dominant negative and constitutively active Ampk in skeletal muscle, we demonstrate that Ulk1 activation is dependent on Ampk. Furthermore, exercise-induced metabolic adaptation requires Ulk1. These findings provide direct evidence of exercise-induced mitophagy and demonstrate the importance of Ampk-Ulk1 signaling in skeletal muscle.Exercise is associated with biogenesis and removal of dysfunctional mitochondria. Here the authors use a mitochondrial reporter gene to demonstrate the occurrence of mitophagy following exercise in mice, and show this is dependent on AMPK and ULK1 signaling.
Details
- Title: Subtitle
- Ampk phosphorylation of Ulk1 is required for targeting of mitochondria to lysosomes in exercise-induced mitophagy
- Creators
- Rhianna C Laker - University of VirginiaJoshua C Drake - University of VirginiaRebecca J Wilson - University of VirginiaVitor A Lira - University of IowaBevan M Lewellen - University of VirginiaKaren A Ryall - University of VirginiaCarleigh C Fisher - University of VirginiaMei Zhang - University of VirginiaJeffrey J Saucerman - University of VirginiaLaurie J Goodyear - Brigham and Women's HospitalMondira Kundu - St. Jude Children's Research HospitalZhen Yan - University of Virginia
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.8(1), 548
- DOI
- 10.1038/s41467-017-00520-9
- PMID
- 28916822
- PMCID
- PMC5601463
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Grant note
- R01 HL114697 / NHLBI NIH HHS R01 AR050429 / NIAMS NIH HHS P30 DK036836 / NIDDK NIH HHS R01 DK101043 / NIDDK NIH HHS
- Language
- English
- Date published
- 09/15/2017
- Academic Unit
- Health, Sport, and Human Physiology
- Record Identifier
- 9984259652102771
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