Optimal HSF1 activation in response to acute cold stress in BAT requires nuclear TXNIP

• Published in: iScience Vol. 26; no. 5; p. 106538
• Main Authors: Waldhart, Althea N., Lau, Kin H., Dykstra, Holly, Avequin, Tracey, Wu, Ning
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.05.2023; Elsevier
• Subjects: Biological sciences; Molecular biology; Molecular interaction; Physiology; Molecular interaction; Biological sciences; Physiology; Molecular biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.106538

While TXNIP (thioredoxin interacting protein) in the plasma membrane and vesicular location is known to negatively regulate cellular glucose uptake by facilitating glucose transporter endocytosis, the function of TXNIP in the nucleus is far less understood. Herein, we sought to determine the function of nuclear TXNIP in vivo, using a new HA-tagged TXNIP knock-in mouse model. We observed that TXNIP can be found in the nucleus of a variety of cells from different tissues including hepatocytes (liver), enterocytes (small intestine), exocrine cells (pancreas), and brown adipocytes (BAT). Further investigations into the role of nuclear TXNIP in BAT revealed that cold stress rapidly and transiently activated HSF1 (heat shock factor 1). HSF1 interaction with TXNIP during its activation is required for optimal HSF1 directed cold shock response in BAT. [Display omitted] •TXNIP nuclear localization is dynamic•Multiple cell types contain nuclear TXNIP in vivo•Nuclear TXNIP is required for optimal activation of HSF1 by cold in BAT Biological sciences; Physiology; Molecular biology; Molecular interaction