Lifelong Ulk1-Mediated Autophagy Deficiency in Muscle Induces Mitochondrial Dysfunction and Contractile Weakness.
Adult
Aged
Aged, 80 and over
Aging
/ metabolism
Animals
Autophagosomes
/ metabolism
Autophagy
/ genetics
Autophagy-Related Protein-1 Homolog
/ deficiency
Female
Humans
Intracellular Signaling Peptides and Proteins
/ metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Mitochondria
/ metabolism
Muscle Contraction
/ genetics
Muscle Fibers, Skeletal
/ metabolism
Muscle Weakness
/ metabolism
Neuromuscular Junction
/ metabolism
Phosphorylation
/ genetics
Reactive Oxygen Species
/ metabolism
Signal Transduction
/ genetics
Young Adult
aging
autophagy flux
mitophagy
neuromuscular junction
sarcopenia
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
16 Feb 2021
16 Feb 2021
Historique:
received:
06
01
2021
revised:
24
01
2021
accepted:
28
01
2021
entrez:
6
3
2021
pubmed:
7
3
2021
medline:
27
4
2021
Statut:
epublish
Résumé
The accumulation of damaged mitochondria due to insufficient autophagy has been implicated in the pathophysiology of skeletal muscle aging. Ulk1 is an autophagy-related kinase that initiates autophagosome assembly and may also play a role in autophagosome degradation (i.e., autophagy flux), but the contribution of Ulk1 to healthy muscle aging is unclear. Therefore, the purpose of this study was to investigate the role of Ulk1-mediated autophagy in skeletal muscle aging. At age 22 months (80% survival rate), muscle contractile and metabolic function were assessed using electrophysiology in muscle-specific Ulk1 knockout mice (MKO) and their littermate controls (LM). Specific peak-isometric torque of the ankle dorsiflexors (normalized by tibialis anterior muscle cross-sectional area) and specific force of the fast-twitch extensor digitorum longus muscles was reduced in MKO mice compared to LM mice (
Identifiants
pubmed: 33669246
pii: ijms22041937
doi: 10.3390/ijms22041937
pmc: PMC7919824
pii:
doi:
Substances chimiques
Intracellular Signaling Peptides and Proteins
0
Reactive Oxygen Species
0
Autophagy-Related Protein-1 Homolog
EC 2.7.11.1
ULK1 protein, human
EC 2.7.11.1
Ulk1 protein, mouse
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : U.S. Department of Defense
ID : W81XWH-18-1-0710
Organisme : National Science Foundation
ID : DGE-1650441
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