Endoplasmic reticulum-associated degradation regulates mitochondrial dynamics in brown adipocytes

Zhangsen Zhou, Mauricio Torres, Haibo Sha, Christopher J. Halbrook, Françoise 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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)54-60
JournalScience
Volume368
Issue number6486
DOIs
Publication statusPublished - 3 Apr 2020

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