p62 links ?-adrenergic input to mitochondrial function and thermogenesis.

Müller, Timo D; Lee, Sang Jun; Jastroch, Martin; Kabra, Dhiraj; Stemmer, Kerstin; Aichler, Michaela; Abplanalp, Bill; Ananthakrishnan, Gayathri; Bhardwaj, Nakul; Collins, Sheila; Divanovic, Senad; Endele, Max; Finan, Brian; Gao, Yuanqing; Habegger, Kirk M; Hembree, Jazzmin; Heppner, Kristy M; Hofmann, Susanna; Holland, Jenna; Küchler, Daniela; Kutschke, Maria; Krishna, Radha; Lehti, Maarit; Oelkrug, Rebecca; Ottaway, Nickki; Perez-Tilve, Diego; Raver, Christine; Walch, Axel K; Schriever, Sonja C; Speakman, John; Tseng, Yu-Hua; Diaz-Meco, Maria; Pfluger, Paul T; Moscat, Jorge; Tschöp, Matthias H     «

Müller, Timo D; Lee, Sang Jun; Jastroch, Martin; Kabra, Dhiraj; Stemmer, Kerstin; Aichler, Michaela; Abplanalp, Bill; Ananthakrishnan, Gayathri; Bhardwaj, Nakul; Collins, Sheila; Divanovic, Senad; Endele, Max; Finan, Brian; Gao, Yuanqing; Habegger, Kirk M; Hembree, Jazzmin; Heppner, Kristy M; Hofmann, Susanna; Holland, Jenna; Küchler, Daniela; Kutschke, Maria; Krishna, Radha; Lehti, Maarit; Oelkrug, Rebecca; Ottaway, Nickki; Perez-Tilve, Diego; Raver, Christine; Walch, Axel K; Schriever, Sonja C...     »

The scaffold protein p62 (sequestosome 1; SQSTM1) is an emerging key molecular link among the metabolic, immune, and proliferative processes of the cell. Here, we report that adipocyte-specific, but not CNS-, liver-, muscle-, or myeloid-specific p62-deficient mice are obese and exhibit a decreased metabolic rate caused by impaired nonshivering thermogenesis. Our results show that p62 regulates energy metabolism via control of mitochondrial function in brown adipose tissue (BAT). Accordingly, adipocyte-specific p62 deficiency led to impaired mitochondrial function, causing BAT to become unresponsive to ?-adrenergic stimuli. Ablation of p62 leads to decreased activation of p38 targets, affecting signaling molecules that control mitochondrial function, such as ATF2, CREB, PGC1?, DIO2, NRF1, CYTC, COX2, ATP5?, and UCP1. p62 ablation in HIB1B and BAT primary cells demonstrated that p62 controls thermogenesis in a cell-autonomous manner, independently of brown adipocyte development or differentiation. Together, our data identify p62 as a novel regulator of mitochondrial function and brown fat thermogenesis.     «

The scaffold protein p62 (sequestosome 1; SQSTM1) is an emerging key molecular link among the metabolic, immune, and proliferative processes of the cell. Here, we report that adipocyte-specific, but not CNS-, liver-, muscle-, or myeloid-specific p62-deficient mice are obese and exhibit a decreased metabolic rate caused by impaired nonshivering thermogenesis. Our results show that p62 regulates energy metabolism via control of mitochondrial function in brown adipose tissue (BAT). Accordingly, ad...     »