A cleavage product of Polycystin-1 is a mitochondrial matrix protein that affects mitochondria morphology and function when heterologously expressed.
A cleavage product of Polycystin-1 is a mitochondrial matrix protein that affects mitochondria morphology and function when heterologously expressed.
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DOI：
10.1038/s41598-018-20856-6
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发表时间：
2018-02-09
影响因子：
4.6
通讯作者：
Germino GG
中科院分区：
文献类型：
--
作者：
Lin CC;Kurashige M;Liu Y;Terabayashi T;Ishimoto Y;Wang T;Choudhary V;Hobbs R;Liu LK;Lee PH;Outeda P;Zhou F;Restifo NP;Watnick T;Kawano H;Horie S;Prinz W;Xu H;Menezes LF;Germino GG
最近的研究报道了Pkd 1基因敲除细胞的内在代谢重编程，暗示多囊肾疾病的发病机制中的细胞代谢失调。然而，代谢变化的确切性质及其根本原因仍然存在争议。我们在此表明，Pkd 1 ko/ko肾上皮细胞有受损的脂肪酸利用，异常的线粒体形态和功能，并在ADPKD患者的肾脏线粒体有形态学改变。我们进一步表明，多囊蛋白-1（CTT）的C-末端裂解产物易位到线粒体基质，CTT在Pkd 1 ko/ko细胞中的表达挽救了一些线粒体表型。使用果蝇模型在体内的影响，我们发现，转基因表达的小鼠CTT的结果在降低生存能力和运动耐力，但增加CO2的产生，与线粒体功能的改变一致。我们的研究结果表明，PC 1可能在调节线粒体功能和细胞代谢中发挥直接作用，并提供了一个框架，以了解受损的线粒体功能如何在生理和病理条件下与肾小管直径的调节有关。
Recent studies have reported intrinsic metabolic reprogramming in Pkd1 knock-out cells, implicating dysregulated cellular metabolism in the pathogenesis of polycystic kidney disease. However, the exact nature of the metabolic changes and their underlying cause remains controversial. We show herein that Pkd1ko/ko renal epithelial cells have impaired fatty acid utilization, abnormal mitochondrial morphology and function, and that mitochondria in kidneys of ADPKD patients have morphological alterations. We further show that a C-terminal cleavage product of polycystin-1 (CTT) translocates to the mitochondria matrix and that expression of CTT in Pkd1ko/ko cells rescues some of the mitochondrial phenotypes. Using Drosophila to model in vivo effects, we find that transgenic expression of mouse CTT results in decreased viability and exercise endurance but increased CO2 production, consistent with altered mitochondrial function. Our results suggest that PC1 may play a direct role in regulating mitochondrial function and cellular metabolism and provide a framework to understand how impaired mitochondrial function could be linked to the regulation of tubular diameter in both physiological and pathological conditions.
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影响因子：
48
作者：
Huber W;Carey VJ;Gentleman R;Anders S;Carlson M;Carvalho BS;Bravo HC;Davis S;Gatto L;Girke T;Gottardo R;Hahne F;Hansen KD;Irizarry RA;Lawrence M;Love MI;MacDonald J;Obenchain V;Oleś AK;Pagès H;Reyes A;Shannon P;Smyth GK;Tenenbaum D;Waldron L;Morgan M
通讯作者：
Morgan M
影响因子：
4.5
作者：
Grampa V;Delous M;Zaidan M;Odye G;Thomas S;Elkhartoufi N;Filhol E;Niel O;Silbermann F;Lebreton C;Collardeau-Frachon S;Rouvet I;Alessandri JL;Devisme L;Dieux-Coeslier A;Cordier MP;Capri Y;Khung-Savatovsky S;Sigaudy S;Salomon R;Antignac C;Gubler MC;Benmerah A;Terzi F;Attié-Bitach T;Jeanpierre C;Saunier S
通讯作者：
Saunier S
影响因子：
15.9
作者：
Chauvet, V;Tian, X;Caplan, MJ
通讯作者：
Caplan, MJ
影响因子：
3.3
作者：
Chen Z;Qi Y;French S;Zhang G;Covian Garcia R;Balaban R;Xu H
通讯作者：
Xu H
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM