Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy.
AMPK
exercise
mitochondria
mitophagy
skeletal muscle
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
14 09 2021
14 09 2021
Historique:
accepted:
05
08
2021
received:
06
08
2021
entrez:
8
9
2021
pubmed:
9
9
2021
medline:
15
12
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34493662
pii: 2025932118
doi: 10.1073/pnas.2025932118
pmc: PMC8449344
pii:
doi:
Substances chimiques
AMPK alpha2 subunit, mouse
EC 2.7.11.1
AMP-Activated Protein Kinases
EC 2.7.11.31
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR050429
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR077440
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR025616
Pays : United States
Organisme : NIA NIH HHS
ID : R00 AG057825
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG067048
Pays : United States
Organisme : NIA NIH HHS
ID : K99 AG057825
Pays : United States
Organisme : NHLBI NIH HHS
ID : R25 HL088724
Pays : United States
Organisme : Wellcome Trust
ID : 204766/Z/16/Z
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL136314
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIH HHS
ID : S10 OD016446
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007284
Pays : United States
Informations de copyright
Copyright © 2021 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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