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Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis

ABSTRACT: 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 eIF2α mediated stress response. The pivotal role of eIF2α is scrutinized by in vivo CRISPR deletion of eIF2α 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.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brown Adipose Tissue

SUBMITTER: Juan A Lopez

LAB HEAD: Juan A Lopez

PROVIDER: PXD057026 | Pride | 2024-11-13

REPOSITORIES: Pride

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			Action	DRS
	JAL_GSB_Bea_BAT_TMTp_003ok.msf	Msf
	JAL_GSB_Bea_BAT_TMTp_Fr1.raw	Raw
	JAL_GSB_Bea_BAT_TMTp_Fr135.raw	Raw
	JAL_GSB_Bea_BAT_TMTp_Fr2.raw	Raw
	JAL_GSB_Bea_BAT_TMTp_Fr246.raw	Raw

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