Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

A tuberous sclerosis complex signalling node at the peroxisome regulates mTORC1 and autophagy in response to ROS

Zhang, Jiangwei, Kim, Jinhee, Alexander, Angela, Cai, Shengli, Tripathi, Durga Nand, Dere, Ruhee, Tee, Andrew, Tait-Mulder, Jacqueline, Di Nardo, Alessia, Han, Juliette M., Kwiatkowski, Erica, Dunlop, Elaine A., Dodd, Kayleigh M., Folkerth, Rebecca D., Faust, Phyllis L., Kastan, Michael B., Sahin, Mustafa and Walker, Cheryl Lyn 2013. A tuberous sclerosis complex signalling node at the peroxisome regulates mTORC1 and autophagy in response to ROS. Nature Cell Biology 15 (10) , pp. 1186-1195. 10.1038/ncb2822

Full text not available from this repository.

Abstract

Subcellular localization is emerging as an important mechanism for mTORC1 regulation. We report that the tuberous sclerosis complex (TSC) signalling node, TSC1, TSC2 and Rheb, localizes to peroxisomes, where it regulates mTORC1 in response to reactive oxygen species (ROS). TSC1 and TSC2 were bound by peroxisomal biogenesis factors 19 and 5 (PEX19 and PEX5), respectively, and peroxisome-localized TSC functioned as a Rheb GTPase-activating protein (GAP) to suppress mTORC1 and induce autophagy. Naturally occurring pathogenic mutations in TSC2 decreased PEX5 binding, and abrogated peroxisome localization, Rheb GAP activity and suppression of mTORC1 by ROS. Cells lacking peroxisomes were deficient in mTORC1 repression by ROS, and peroxisome-localization-deficient TSC2 mutants caused polarity defects and formation of multiple axons in neurons. These data identify a role for the TSC in responding to ROS at the peroxisome, and identify the peroxisome as a signalling organelle involved in regulation of mTORC1.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Nature
ISSN: 1465-7392
Last Modified: 13 Sep 2019 21:45
URI: http://orca.cf.ac.uk/id/eprint/51388

Citation Data

Cited 85 times in Google Scholar. View in Google Scholar

Cited 124 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item