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

doi:10.1126/science.aay2494

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

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 language	English (US)
Article number	aay2494
Journal	Science
Volume	368
Issue number	6486
DOIs	https://doi.org/10.1126/science.aay2494
State	Published - Apr 3 2020

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Zhou, Z., Torres, M., Sha, H., Halbrook, C. J., van den Bergh, F., Reinert, R. B., Yamada, T., Wang, S., Luo, Y., Hunter, A. H., Wang, C., Sanderson, T. H., Liu, M., Taylor, A., Sesaki, H., Lyssiotis, C. A., Wu, J., Kersten, S., Beard, D. A., & Qi, L. (2020). Endoplasmic reticulum-associated degradation regulates mitochondrial dynamics in brown adipocytes. Science, 368(6486), Article aay2494. https://doi.org/10.1126/science.aay2494

Zhou, Z, Torres, M, Sha, H, Halbrook, CJ, van den Bergh, F, Reinert, RB, Yamada, T, Wang, S, Luo, Y, Hunter, AH, Wang, C, Sanderson, TH, Liu, M, Taylor, A, Sesaki, H, Lyssiotis, CA, Wu, J, Kersten, S, Beard, DA & Qi, L 2020, 'Endoplasmic reticulum-associated degradation regulates mitochondrial dynamics in brown adipocytes', Science, vol. 368, no. 6486, aay2494. https://doi.org/10.1126/science.aay2494

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title = "Endoplasmic reticulum-associated degradation regulates mitochondrial dynamics in brown adipocytes",

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.",

author = "Zhangsen Zhou and Mauricio Torres and Haibo Sha and Halbrook, {Christopher J.} and {van den Bergh}, Fran{\c c}oise and Reinert, {Rachel B.} and Tatsuya Yamada and Siwen Wang and Yingying Luo and Hunter, {Allen H.} and Chunqing Wang and Sanderson, {Thomas H.} and Meilian Liu and Aaron Taylor and Hiromi Sesaki and Lyssiotis, {Costas A.} and Jun Wu and Sander Kersten and Beard, {Daniel A.} and Ling Qi",

year = "2020",

month = apr,

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doi = "10.1126/science.aay2494",

language = "English (US)",

volume = "368",

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AU - Zhou, Zhangsen

AU - Torres, Mauricio

AU - Sha, Haibo

AU - Halbrook, Christopher J.

AU - van den Bergh, Françoise

AU - Reinert, Rachel B.

AU - Yamada, Tatsuya

AU - Wang, Siwen

AU - Luo, Yingying

AU - Hunter, Allen H.

AU - Wang, Chunqing

AU - Sanderson, Thomas H.

AU - Liu, Meilian

AU - Taylor, Aaron

AU - Sesaki, Hiromi

AU - Lyssiotis, Costas A.

AU - Wu, Jun

AU - Kersten, Sander

AU - Beard, Daniel A.

AU - Qi, Ling

PY - 2020/4/3

Y1 - 2020/4/3

N2 - 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.

AB - 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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Endoplasmic reticulum-associated degradation regulates mitochondrial dynamics in brown adipocytes

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