Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis

被引：0

作者：

Cicuendez, Beatriz ^{[1
,2
]}

Mora, Alfonso ^{[1
,2
]}

Lopez, Juan Antonio ^{[1
,3
]}

Curtabbi, Andrea ^{[1
,4
]}

Perez-Garcia, Javier ^{[2
]}

Porteiro, Begona ^{[5
,6
]}

Jimenez-Blasco, Daniel ^{[4
,7
,8
]}

Latorre-Muro, Pedro ^{[9
,10
]}

Vo, Paula ^{[11
]}

Jerome, Madison ^{[11
]}

Gomez-Santos, Beatriz ^{[12
]}

Romero-Becerra, Rafael ^{[1
]}

Leiva, Magdalena ^{[13
]}

Rodriguez, Elena ^{[1
,2
]}

Leon, Marta ^{[1
,2
]}

Leiva-Vega, Luis ^{[1
,2
]}

Gomez-Lado, Noemi ^{[14
,15
,16
]}

Torres, Jorge L. ^{[17
]}

Hernandez-Cosido, Lourdes ^{[18
]}

Aguiar, Pablo ^{[14
,15
,16
]}

Marcos, Miguel ^{[19
,20
]}

Jastroch, Martin ^{[21
]}

Daiber, Andreas ^{[22
,23
]}

Aspichueta, Patricia ^{[12
,24
]}

Bolanos, Juan Pedro ^{[4
,7
,8
]}

Spinelli, Jessica B. ^{[11
,25
]}

Puigserver, Pere ^{[9
,10
]}

Enriquez, Jose Antonio ^{[1
,4
]}

Vazquez, Jesus ^{[1
,3
]}

Folgueira, Cintia ^{[1
,2
,6
]}

Sabio, Guadalupe ^{[1
,2
]}

机构：

[1] Ctr Nacl Invest Cardiovasc CNIC, Madrid, Spain

[2] Spanish Natl Canc Ctr CNIO, Mol Oncol Program, Organ Crosstalk Metab Dis Grp, Madrid, Spain

[3] Inst Salud Carlos III, CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain

[4] Inst Salud Carlos III, Ctr Invest Biomed Red Fragil & Envejecimiento Salu, Madrid, Spain

[5] Univ Santiago Compostela, CIMUS, Dept Physiol, Santiago De Compostela, Spain

[6] Inst Salud Carlos III, CIBER Fisiopatol Obes & Nutr CIBERObn, Madrid, Spain

[7] Univ Salamanca, CSIC, Inst Funct Biol & Genom, Salamanca, Spain

[8] Univ Salamanca, Univ Hosp Salamanca, CSIC, Inst Biomed Res Salamanca, Salamanca, Spain

[9] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA

[10] Harvard Med Sch, Dept Cell Biol, Boston, MA USA

[11] UMass Chan Med Sch, Program Mol Med, Worcester, MA USA

[12] Univ Basque Country, UPV EHU Leioa, Biobizkaia Hlth Res Inst, Dept Physiol,Fac Med & Nursing, Leioa, Bizkaia, Spain

[13] Univ Complutense Madrid, Sch Med, Dept Immunol, Madrid, Spain

[14] Univ Santiago Compostela USC, Ctr Res Mol Med & Chron Dis CiMUS, Mol Imaging Biomarkers & Theragnosis Lab, Santiago De Compostela, Spain

[15] Hlth Res Inst Santiago Compostela IDIS, Mol Imaging Grp, Santiago De Compostela, Spain

[16] Univ Clin Hosp Santiago Compostela CHUS, Complejo Hosp, Santiago De Compostela, Spain

[17] Complejo Asistencial Zamora, Zamora, Spain

[18] Univ Salamanca, Univ Hosp Salamanca, Bariatr Surg Unit, Dept Gen Surg,Dept Surg, Salamanca, Spain

[19] Univ Hosp Salamanca, IBSAL, Dept Internal Med, Salamanca, Spain

[20] Univ Salamanca, Dept Med, Salamanca, Spain

[21] Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden

[22] Univ Med Ctr Mainz, Dept Cardiol, Mainz, Germany

[23] German Ctr Cardiovasc Res DZHK, Partner Site Rhine Main, Mainz, Germany

[24] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid 28029, Spain

[25] UMASS Chan Med Sch, Canc Ctr, Worcester, MA USA

来源：

NATURE COMMUNICATIONS | 2025年 / 16卷 / 01期

关键词：

FAT THERMOGENESIS; ENDOCRINE ROLE; TRANSPLANTATION; MICE; METABOLISM; ACTIVATION; PATHWAY; DISEASE; PROTEIN; OBESITY;

D O I：

10.1038/s41467-024-54353-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Obesity poses a global health challenge, demanding a deeper understanding of adipose tissue (AT) and its mitochondria. This study describes the role of the mitochondrial protein Methylation-controlled J protein (MCJ/DnaJC15) in orchestrating brown adipose tissue (BAT) thermogenesis. Here we show how MCJ expression decreases during obesity, as evident in human and mouse adipose tissue samples. MCJKO mice, even without UCP1, a fundamental thermogenic protein, exhibit elevated BAT thermogenesis. Electron microscopy unveils changes in mitochondrial morphology resembling BAT activation. Proteomic analysis confirms these findings and suggests involvement of the eIF2 alpha mediated stress response. The pivotal role of eIF2 alpha is scrutinized by in vivo CRISPR deletion of eIF2 alpha in MCJKO mice, abrogating thermogenesis. These findings uncover the importance of MCJ as a regulator of BAT thermogenesis, presenting it as a promising target for obesity therapy.

引用

页数：16

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