ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1

Seong Keun Sonn, Seungwoon Seo, Jaemoon Yang, Ki Sook Oh, Hsiuchen Chen, David C. Chan, Kunsoo Rhee, Kyung S. Lee, Young Yang, Goo Taeg Oh

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish
Pages (from-to)1769-1780
Number of pages12
JournalExperimental and Molecular Medicine
Volume53
Issue number11
DOIs
StatePublished - Nov 2021

Bibliographical note

Funding Information:
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (Nos. 2021M3E5E7023628, 2020R1A3B2079811 and 2018R1D1A1B07050561).

Publisher Copyright:
© 2021, The Author(s).

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