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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-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 language	English
Pages (from-to)	54-60
Journal	Science
Volume	368
Issue number	6486
DOIs	https://doi.org/10.1126/science.aay2494
Publication status	Published - 3 Apr 2020

Access to Document

10.1126/science.aay2494

Fingerprint Dive into the research topics of 'Endoplasmic reticulum-associated degradation regulates mitochondrial dynamics in brown adipocytes'. Together they form a unique fingerprint.

Regulation of endoplasmic reticulum-mitochondria contacts and mitochondrial dynamics by Sel1L-Hrd1 ERAD during thermogenesis
Zhou, Z. (Creator), Torres, M. (Creator), Sha, H. (Creator), Halbrook, C. J. (Creator), van den Bergh, F. (Creator), Reinert, R. B. (Creator), Yamada, T. (Creator), Wang, S. (Creator), Luo, Y. (Creator), Hunter, A. H. (Creator), Wang, C. (Creator), Sanderson, T. H. (Creator), Liu, M. (Creator), Taylor, A. (Creator), Sesaki, H. (Creator), Lyssiotis, C. A. (Creator), Wu, J. (Creator), Kersten, S. (Creator), Beard, D. A. (Creator) & Qi, L. (Creator), Wageningen University, 24 Apr 2020
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE145895
Dataset

Cite this

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), 54-60. https://doi.org/10.1126/science.aay2494

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. / Endoplasmic reticulum-associated degradation regulates mitochondrial dynamics in brown adipocytes. In: Science. 2020 ; Vol. 368, No. 6486. pp. 54-60.

@article{687f942316a24afc94e1131d01d86a4a,

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,

day = "3",

doi = "10.1126/science.aay2494",

language = "English",

volume = "368",

pages = "54--60",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6486",

}

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, pp. 54-60. https://doi.org/10.1126/science.aay2494

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.

In: Science, Vol. 368, No. 6486, 03.04.2020, p. 54-60.

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

TY - JOUR

T1 - Endoplasmic reticulum-associated degradation regulates mitochondrial dynamics in brown adipocytes

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.

U2 - 10.1126/science.aay2494

DO - 10.1126/science.aay2494

M3 - Article

C2 - 32193362

AN - SCOPUS:85082977920

VL - 368

SP - 54

EP - 60

JO - Science

JF - Science

SN - 0036-8075

IS - 6486

ER -

Endoplasmic reticulum-associated degradation regulates mitochondrial dynamics in brown adipocytes

Abstract

Access to Document

Regulation of endoplasmic reticulum-mitochondria contacts and mitochondrial dynamics by Sel1L-Hrd1 ERAD during thermogenesis

Cite this