CBL/CAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells.
CBL
SORBS1
glucose transport
insulin resistance
insulin signalling
mitochondria
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:
08 Feb 2023
08 Feb 2023
Historique:
received:
04
01
2023
revised:
02
02
2023
accepted:
04
02
2023
entrez:
25
2
2023
pubmed:
26
2
2023
medline:
3
3
2023
Statut:
epublish
Résumé
CBL is rapidly phosphorylated upon insulin receptor activation. Mice whole body CBL depletion improved insulin sensitivity and glucose clearance; however, the precise mechanisms remain unknown. We depleted either CBL or its associated protein SORBS1/CAP independently in myocytes and assessed mitochondrial function and metabolism compared to control cells. CBL- and CAP-depleted cells showed increased mitochondrial mass with greater proton leak. Mitochondrial respiratory complex I activity and assembly into respirasomes were reduced. Proteome profiling revealed alterations in proteins involved in glycolysis and fatty acid degradation. Our findings demonstrate CBL/CAP pathway couples insulin signaling to efficient mitochondrial respiratory function and metabolism in muscle.
Identifiants
pubmed: 36834818
pii: ijms24043399
doi: 10.3390/ijms24043399
pmc: PMC9964740
pii:
doi:
Substances chimiques
Insulin
0
Proto-Oncogene Proteins c-cbl
EC 2.3.2.27
Cbl protein, mouse
EC 6.3.2.-
ponsin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : MC_UU_00014/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00014/5
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : R01 GM105781
Pays : United States
Organisme : British Heart Foundation
ID : RG/18/7/33636
Pays : United Kingdom
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