التفاصيل البيبلوغرافية
| العنوان: |
Parkin controls brown adipose tissue plasticity in response to adaptive thermogenesis. |
| المؤلفون: |
Cairó, Montserrat, Campderrós, Laura, Gavaldà‐Navarro, Aleix, Cereijo, Rubén, Delgado‐Anglés, Alejandro, Quesada‐López, Tania, Giralt, Marta, Villarroya, Joan, Villarroya, Francesc |
| المصدر: |
EMBO Reports; May2019, Vol. 20 Issue 5, pN.PAG-N.PAG, 1p |
| مستخلص: |
Parkin is an ubiquitin‐E3 ligase that acts as a key component of the cellular machinery for mitophagy. We show here that Parkin expression is reciprocally regulated in brown adipose tissue in relation to thermogenic activity. Thermogenic stimuli repress Parkin gene expression via transcriptional mechanisms that are elicited by noradrenergic and PPARα‐mediated pathways that involve intracellular lipolysis in brown adipocytes. Parkin‐KO mice show over‐activated brown adipose tissue thermogenic activity and exhibit improved metabolic parameters, especially when fed a high‐fat diet. Deacclimation, which is the return of a cold‐adapted mouse to a thermoneutral temperature, dramatically induces mitophagy in brown adipocytes, with a concomitant induction of Parkin levels. We further reveal that Parkin‐KO mice exhibit defects in the degradative processing of mitochondrial proteins in brown adipose tissue in response to deacclimation. These results suggest that the transcriptional control of Parkin in brown adipose tissue may contribute to modulating the mitochondrial mass and activity for adaptation to thermogenic requirements. Synopsis: Parkin, a key protein in mitochondrial homeostasis, promotes the adaptive physiological plasticity of brown adipose tissue in response to thermogenic challenges. Thermogenic activation of brown adipose tissue leads to transcriptional repression of Parkin through pathways involving PPARα.The absence of Parkin leads to brown adipose tissue over‐activation.Parkin facilitates adaptive intracellular remodeling associated with brown adipocyte thermogenic inactivation. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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