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ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1

Sonn, Seong Keun and Seo, Seungwoon and Yang, Jaemoon and Oh, Ki Sook and Chen, Hsiuchen and Chan, David C. and Rhee, Kunsoo and Lee, Kyung S. and Yang, Young and Oh, Goo Taeg (2021) ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1. Experimental and Molecular Medicine, 53 . pp. 1769-1780. ISSN 1226-3613. PMCID PMC8639813. doi:10.1038/s12276-021-00701-z. https://resolver.caltech.edu/CaltechAUTHORS:20211129-367530900

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Abstract

C1q/TNF-related protein 1 (CTRP1) is a CTRP family member that has collagenous and globular C1q-like domains. The secreted form of CTRP1 is known to be associated with cardiovascular and metabolic diseases, but its cellular roles have not yet been elucidated. Here, we showed that cytosolic CTRP1 localizes to the endoplasmic reticulum (ER) membrane and that knockout or depletion of CTRP1 leads to mitochondrial fission defects, as demonstrated by mitochondrial elongation. Mitochondrial fission events are known to occur through an interaction between mitochondria and the ER, but we do not know whether the ER and/or its associated proteins participate directly in the entire mitochondrial fission event. Interestingly, we herein showed that ablation of CTRP1 suppresses the recruitment of DRP1 to mitochondria and provided evidence suggesting that the ER–mitochondrion interaction is required for the proper regulation of mitochondrial morphology. We further report that CTRP1 inactivation-induced mitochondrial fission defects induce apoptotic resistance and neuronal degeneration, which are also associated with ablation of DRP1. These results demonstrate for the first time that cytosolic CTRP1 is an ER transmembrane protein that acts as a key regulator of mitochondrial fission, providing new insight into the etiology of metabolic and neurodegenerative disorders.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/s12276-021-00701-zDOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639813PubMed CentralArticle
https://static-content.springer.com/esm/art%3A10.1038%2Fs12276-021-00701-z/MediaObjects/12276_2021_701_MOESM1_ESM.pdfPublisherSupplementary material
ORCID:
AuthorORCID
Chan, David C.0000-0002-0191-2154
Rhee, Kunsoo0000-0002-5051-876X
Oh, Goo Taeg0000-0002-1104-1698
Additional Information:© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received 20 May 2021. Revised 03 September 2021. Accepted 07 September 2021. Published 26 November 2021. This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (Nos. 2021M3E5E7023628, 2020R1A3B2079811 and 2018R1D1A1B07050561). Contributions. Conceptualization: S.K.S., Y.Y., and G.T.O.; Methodology, formal analysis, and writing – original draft: S.K.S. and G.T.O.; Investigation: S.K.S., S.S., and J.Y.; Writing – review and editing: G.T.O., H.C., D.C.C., K.R., and K.S.L.; Funding acquisition and supervision: G.T.O. The authors declare no competing interests.
Funders:
Funding AgencyGrant Number
National Research Foundation of Korea2021M3E5E7023628
National Research Foundation of Korea2020R1A3B2079811
National Research Foundation of Korea2018R1D1A1B07050561
PubMed Central ID:PMC8639813
DOI:10.1038/s12276-021-00701-z
Record Number:CaltechAUTHORS:20211129-367530900
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20211129-367530900
Official Citation:Sonn, S.K., Seo, S., Yang, J. et al. ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1. Exp Mol Med 53, 1769–1780 (2021). https://doi.org/10.1038/s12276-021-00701-z
ID Code:112059
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:29 Nov 2021 08:59
Last Modified:26 Oct 2022 18:30

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  • ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1. (deposited 29 Nov 2021 08:59) [Currently Displayed]

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  • Sonn, Seong Keun and Seo, Seungwoon and Yang, Jaemoon and Oh, Ki Sook and Chen, Hsiuchen and Chan, David C. and Rhee, Kunsoo and Lee, Kyung S. and Yang, Young and Oh, Goo Taeg ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1. (deposited 29 Nov 2021 08:59) [Currently Displayed]

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