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Endoplasmic reticulum–associated degradation regulates mitochondrial dynamics in brown adipocytes
- Zhou, Zhangsen;
- Torres, Mauricio;
- Sha, Haibo;
- Halbrook, Christopher J;
- Van den Bergh, Françoise;
- 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
- et al.
Published Web Location
https://doi.org/10.1126/science.aay2494Abstract
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.
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