ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1.
ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1.
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DOI：
10.1038/s12276-021-00701-z
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发表时间：
2021-11
影响因子：
12.8
通讯作者：
Oh GT
中科院分区：
文献类型：
--
作者：
Sonn SK;Seo S;Yang J;Oh KS;Chen H;Chan DC;Rhee K;Lee KS;Yang Y;Oh GT
C1 q/TNF相关蛋白1（C1 q/TNF-related protein 1，CTRP 1）是CTRP家族成员，具有胶原样和球状C1 q样结构域。已知CTRP 1的分泌形式与心血管和代谢疾病相关，但其细胞作用尚未阐明。在这里，我们表明，胞质CTRP 1定位于内质网（ER）膜，CTRP 1的敲除或耗尽导致线粒体分裂缺陷，如线粒体延长所示。线粒体分裂事件是通过线粒体和ER之间的相互作用而发生的，但我们不知道ER和/或其相关蛋白是否直接参与整个线粒体分裂事件。有趣的是，我们在本文中表明，CTRP 1的消融抑制了DRP 1向线粒体的募集，并提供了证据表明ER-配体相互作用是适当调节线粒体形态所必需的。我们进一步报道，CTRP 1失活诱导的线粒体分裂缺陷诱导凋亡抵抗和神经元变性，这也与DRP 1的消融有关。这些结果首次表明，胞质CTRP 1是一种ER跨膜蛋白，作为线粒体分裂的关键调节因子，为代谢和神经退行性疾病的病因学提供了新的见解。一种名为CTRP 1的蛋白质帮助线粒体，细胞的动力，在它们生长过大后分裂，并可以提供对阿尔茨海默病等神经退行性疾病的见解。已知CTRP 1参与代谢和心血管疾病。这一发现也在心肌等富含维生素A的组织中高度表达，这导致韩国梨花女子大学的Goo Taeg Oh和Sookmyung女子大学的Young Yang及其同事进一步研究其功能。他们发现CTRP 1在细胞的运输系统中高度表达，在那里它有助于调节线粒体分裂。CTRP 1缺陷小鼠产生异常长的线粒体，导致细胞对程序性细胞死亡产生抵抗力，并导致神经元变性。这些结果可能会增加对线粒体缺陷相关疾病的理解。
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. A protein named CTRP1 helps mitochondria, the powerhouses of cells, to divide after they grow too big, and could provide insight into neurodegenerative disorders such as Alzheimer’s disease. CTRP1 is known to be involved in metabolic and cardiovascular diseases. The finding that it is also highly expressed in mitochondria-rich tissues such as heart muscle led Goo Taeg Oh at Ewha Womans University and Young Yang at Sookmyung Women’s University, both in South Korea, and coworkers to further investigate its function. They found that CTRP1 is highly expressed in the cell’s transport system, where it helps to regulate mitochondrial division. CTRP1 deficiency in mice produced abnormally long mitochondria, causing cells to become resistant to programmed cell death, and leading to degeneration of neurons. These results may increase understanding of diseases related to mitochondrial defects.
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影响因子：
5.4
作者：
Ma, Xiaoqin;Yu, Meixiang;Yang, Wanhua
通讯作者：
Yang, Wanhua
DOI：
10.1083/jcb.201508099
发表时间：
2016-02-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
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影响因子：
16.8
作者：
通讯作者：
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影响因子：
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作者：
Innamorati, G;Whang, MI;Birnbaumer, M
通讯作者：
Birnbaumer, M
影响因子：
12.8
作者：
Lim Y;Dorstyn L;Kumar S
通讯作者：
Kumar S