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ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1

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 loc...

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Autores principales: Sonn, Seong Keun, Seo, Seungwoon, Yang, Jaemoon, Oh, Ki Sook, Chen, Hsiuchen, Chan, David C., Rhee, Kunsoo, Lee, Kyung S., Yang, Young, Oh, Goo Taeg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639813/
https://www.ncbi.nlm.nih.gov/pubmed/34837016
http://dx.doi.org/10.1038/s12276-021-00701-z
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author Sonn, Seong Keun
Seo, Seungwoon
Yang, Jaemoon
Oh, Ki Sook
Chen, Hsiuchen
Chan, David C.
Rhee, Kunsoo
Lee, Kyung S.
Yang, Young
Oh, Goo Taeg
author_facet Sonn, Seong Keun
Seo, Seungwoon
Yang, Jaemoon
Oh, Ki Sook
Chen, Hsiuchen
Chan, David C.
Rhee, Kunsoo
Lee, Kyung S.
Yang, Young
Oh, Goo Taeg
author_sort Sonn, Seong Keun
collection PubMed
description 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.
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spelling pubmed-86398132021-12-10 ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1 Sonn, Seong Keun Seo, Seungwoon Yang, Jaemoon Oh, Ki Sook Chen, Hsiuchen Chan, David C. Rhee, Kunsoo Lee, Kyung S. Yang, Young Oh, Goo Taeg Exp Mol Med Article 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. Nature Publishing Group UK 2021-11-26 /pmc/articles/PMC8639813/ /pubmed/34837016 http://dx.doi.org/10.1038/s12276-021-00701-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access 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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Sonn, Seong Keun
Seo, Seungwoon
Yang, Jaemoon
Oh, Ki Sook
Chen, Hsiuchen
Chan, David C.
Rhee, Kunsoo
Lee, Kyung S.
Yang, Young
Oh, Goo Taeg
ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1
title ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1
title_full ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1
title_fullStr ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1
title_full_unstemmed ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1
title_short ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1
title_sort er-associated ctrp1 regulates mitochondrial fission via interaction with drp1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639813/
https://www.ncbi.nlm.nih.gov/pubmed/34837016
http://dx.doi.org/10.1038/s12276-021-00701-z
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