CBL/CAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells

Cho-Cho Aye; Dean E Hammond; Sergio Rodriguez-Cuenca; Mary K Doherty; Phillip D Whitfield; Marie M Phelan; Chenjing Yang; Rafael Perez-Perez; Xiaoxin Li; Angels Diaz-Ramos; Gopal Peddinti; Matej Oresic; Antonio Vidal-Puig; Antonio Zorzano; Cristina Ugalde; Silvia Mora

doi:10.3390/ijms24043399

CBL/CAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells

Cho-Cho Aye, Dean E Hammond, Sergio Rodriguez-Cuenca, Mary K Doherty, Phillip D Whitfield, Marie M Phelan, Chenjing Yang, Rafael Perez-Perez, Xiaoxin Li, Angels Diaz-Ramos, Gopal Peddinti, Matej Oresic, Antonio Vidal-Puig, Antonio Zorzano, Cristina Ugalde, Silvia Mora

Turku Bioscience

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Abstract

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.

Original language	English
Journal	International Journal of Molecular Sciences
Volume	24
Issue number	4
DOIs	https://doi.org/10.3390/ijms24043399
Publication status	Published - 8 Feb 2023
MoE publication type	A1 Journal article-refereed

Keywords

Animals
Mice
Energy Metabolism
Insulin/metabolism
Insulin Resistance
Mitochondria/metabolism
Mitochondria, Muscle/metabolism
Muscle Cells/metabolism
Proto-Oncogene Proteins c-cbl/metabolism
Cell Respiration

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10.3390/ijms24043399

ijms-24-03399Final published version, 2.43 MBLicence: CC BY

https://urn.fi/URN:NBN:fi-fe202402167477

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Aye, C.-C., Hammond, D. E., Rodriguez-Cuenca, S., Doherty, M. K., Whitfield, P. D., Phelan, M. M., Yang, C., Perez-Perez, R., Li, X., Diaz-Ramos, A., Peddinti, G., Oresic, M., Vidal-Puig, A., Zorzano, A., Ugalde, C., & Mora, S. (2023). CBL/CAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells. International Journal of Molecular Sciences, 24(4). https://doi.org/10.3390/ijms24043399

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title = "CBL/CAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells",

abstract = "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.",

keywords = "Animals, Mice, Energy Metabolism, Insulin/metabolism, Insulin Resistance, Mitochondria/metabolism, Mitochondria, Muscle/metabolism, Muscle Cells/metabolism, Proto-Oncogene Proteins c-cbl/metabolism, Cell Respiration, CBL, mitochondria, insulin signalling, insulin resistance, glucose transport, SORBS1",

author = "Cho-Cho Aye and Hammond, {Dean E} and Sergio Rodriguez-Cuenca and Doherty, {Mary K} and Whitfield, {Phillip D} and Phelan, {Marie M} and Chenjing Yang and Rafael Perez-Perez and Xiaoxin Li and Angels Diaz-Ramos and Gopal Peddinti and Matej Oresic and Antonio Vidal-Puig and Antonio Zorzano and Cristina Ugalde and Silvia Mora",

year = "2023",

month = feb,

day = "8",

doi = "10.3390/ijms24043399",

language = "English",

volume = "24",

journal = "International Journal of Molecular Sciences",

issn = "1661-6596",

publisher = "MDPI",

number = "4",

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Aye, C-C, Hammond, DE, Rodriguez-Cuenca, S, Doherty, MK, Whitfield, PD, Phelan, MM, Yang, C, Perez-Perez, R, Li, X, Diaz-Ramos, A, Peddinti, G, Oresic, M, Vidal-Puig, A, Zorzano, A, Ugalde, C & Mora, S 2023, 'CBL/CAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells', International Journal of Molecular Sciences, vol. 24, no. 4. https://doi.org/10.3390/ijms24043399

TY - JOUR

T1 - CBL/CAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells

AU - Aye, Cho-Cho

AU - Hammond, Dean E

AU - Rodriguez-Cuenca, Sergio

AU - Doherty, Mary K

AU - Whitfield, Phillip D

AU - Phelan, Marie M

AU - Yang, Chenjing

AU - Perez-Perez, Rafael

AU - Li, Xiaoxin

AU - Diaz-Ramos, Angels

AU - Peddinti, Gopal

AU - Oresic, Matej

AU - Vidal-Puig, Antonio

AU - Zorzano, Antonio

AU - Ugalde, Cristina

AU - Mora, Silvia

PY - 2023/2/8

Y1 - 2023/2/8

N2 - 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.

AB - 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.

KW - Animals

KW - Mice

KW - Energy Metabolism

KW - Insulin/metabolism

KW - Insulin Resistance

KW - Mitochondria/metabolism

KW - Mitochondria, Muscle/metabolism

KW - Muscle Cells/metabolism

KW - Proto-Oncogene Proteins c-cbl/metabolism

KW - Cell Respiration

KW - CBL

KW - mitochondria

KW - insulin signalling

KW - insulin resistance

KW - glucose transport

KW - SORBS1

U2 - 10.3390/ijms24043399

DO - 10.3390/ijms24043399

M3 - Article

C2 - 36834818

SN - 1661-6596

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 4

ER -

CBL/CAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells

Abstract

Keywords

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