|Title||Endoplasmic reticulum-associated degradation regulates mitochondrial dynamics in brown adipocytes|
|Author(s)||Zhou, Zhangsen; Torres, Mauricio; Sha, Haibo; Halbrook, Christopher J.; Bergh, Françoise van den; Reinert, Rachel B.; Yamada, Tatsuya; Wang, Siwen; Luo, Yingying; Hunter, Allen H.; Wang, Chunqing; Sanderson, Thomas H.; Liu, Meilian; Taylor, Aaron; Sesaki, Hiromi; Lyssiotis, Costas A.; Wu, Jun; Kersten, Sander; Beard, Daniel A.; Qi, Ling|
|Source||Science 368 (2020)6486. - ISSN 0036-8075 - p. 54 - 60.|
Nutrition, Metabolism and Genomics
|Publication type||Refereed Article in a scientific journal|
The 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 cross-talk and expands our understanding of the physiological importance of Sel1L-Hrd1 ERAD.