Title: Endoplasmic reticulum–associated degradation regulates mitochondrial dynamics in brown adipocytes
Author: Zhangsen Zhou, Mauricio Torres, Haibo Sha, Christopher J. Halbrook, Franoise Van den Bergh, Rachel B. Reinert, Tatsuya Yamada, Siwen Wang, Yingying Luo, Allen H. Hunter, Chunqing Wang, Thomas H. Sanderson, Meilian Liu, Aaron Taylor, Hiromi Sesaki, Costas A. Lyssiotis, Jun Wu, Sander Kersten, Daniel A. Beard, Ling Qi
Abstract: AbstractThe endoplasmic reticulum (ER) engages mitochondria at specialized ER domains known as mitochondria-associated membranes (MAMs). Here, we used three-dimensional high-resolution imaging to investigate the formation of pleomorphic “megamitochondria” with altered MAMs in brown adipocytes lacking the Sel1L-Hrd1 protein complex of ER-associated protein degradation (ERAD). Mice with ERAD deficiency in brown adipocytes were cold sensitive and exhibited mitochondrial dysfunction. ERAD deficiency affected ER-mitochondria contacts and mitochondrial dynamics, at least in part, by regulating the turnover of the MAM protein, sigma receptor 1 (SigmaR1). Thus, our study provides molecular insights into ER-mitochondrial crosstalk and expands our understanding of the physiological importance of Sel1L-Hrd1 ERAD.