Complex-I Alteration and Enhanced Mitochondrial Fusion Are Associated With Prostate Cancer Progression.
Complex-I Alteration and Enhanced Mitochondrial Fusion Are Associated With Prostate Cancer Progression.
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DOI：
10.1002/jcp.25240
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发表时间：
2016-06
影响因子：
5.6
通讯作者：
Dasgupta S
中科院分区：
文献类型：
--
作者：
Philley JV;Kannan A;Qin W;Sauter ER;Ikebe M;Hertweck KL;Troyer DA;Semmes OJ;Dasgupta S
线粒体（mt）编码的呼吸复合物-I（RCI）突变及其致病性在前列腺癌（PCa）中仍是未知的。关于PCa中mtDNA缺失对线粒体完整性的作用知之甚少。我们确定了人类和小鼠PCa的mtDNA突变，并评估了mtDNA缺失对线粒体完整性的影响。我们还检查了来自PCa患者的循环外泌体是否被转运到mt并携带mtDNA或mt蛋白。我们已经在人类和Hi-myc PCa中采用了下一代全mt基因组测序。测定mtDNA耗竭对血清外泌体中线粒体完整性、mtDNA存在和蛋白质的影响。人PCa细胞和循环外泌体的共培养，随后进行共聚焦成像，确定了外泌体和mt的共定位。我们观察到在人类和Hi-myc PCa中频繁的RCI突变，其破坏相应的复杂蛋白质表达。PCa细胞中mtDNA的缺失影响了线粒体的完整性，增加了MFN 1、MFN 2、PINK 1的表达，降低了MT-TFA的表达。在Hi-myc肿瘤中，mt融合和PINK 1和DNM 1 L表达增加也很明显。在患有良性前列腺增生（BPH）和进行性PCa的男性的循环外泌体中检测到RCI-mtDNA、MFN 2和IMMT蛋白。循环外泌体和mt共定位于PCa细胞中。我们的研究确定了PCa中新的致病性RCI突变，并确定了mtDNA缺失对线粒体完整性的影响。循环外泌体中mtDNA和mt蛋白的存在暗示它们对于生物标志物开发的有用性。
Mitochondria (mt) encoded respiratory complex-I (RCI) mutations and their pathogenicity remain largely unknown in prostate cancer (PCa). Little is known about the role of mtDNA loss on mt integrity in PCa. We determined mtDNA mutation in human and mice PCa and assessed the impact of mtDNA depletion on mt integrity. We also examined whether the circulating exosomes from PCa patients are transported to mt and carry mtDNA or mt proteins. We have employed next generation sequencing of the whole mt genome in human and Hi-myc PCa. The impact of mtDNA depletion on mt integrity, presence of mtDNA, and protein in sera exosomes was determined. A co-culture of human PCa cells and the circulating exosomes followed by confocal imaging determined co-localization of exosomes and mt. We observed frequent RCI mutations in human and Hi-myc PCa which disrupted corresponding complex protein expression. Depletion of mtDNA in PCa cells influenced mt integrity, increased expression of MFN1, MFN2, PINK1, and decreased expression of MT-TFA. Increased mt fusion and expression of PINK1 and DNM1L were also evident in the Hi-myc tumors. RCI-mtDNA, MFN2, and IMMT proteins were detected in the circulating exosomes of men with benign prostate hyperplasia (BPH) and progressive PCa. Circulating exosomes and mt co-localized in PCa cells. Our study identified new pathogenic RCI mutations in PCa and defined the impact of mtDNA loss on mt integrity. Presence of mtDNA and mt proteins in the circulating exosomes implicated their usefulness for biomarker development.
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影响因子：
6.4
作者：
Dasgupta, Santanu;Hoque, Mohammad Obaidul;Upadhyay, Sunil;Sidransky, David
通讯作者：
Sidransky, David
DOI：
10.1158/1940-6207.capr-10-0326
发表时间：
2011-05
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Chatterjee A;Dasgupta S;Sidransky D
通讯作者：
Sidransky D
影响因子：
11.2
作者：
Guo J;Zheng L;Liu W;Wang X;Wang Z;Wang Z;French AJ;Kang D;Chen L;Thibodeau SN;Liu W
通讯作者：
Liu W
DOI：
10.1158/1940-6207.capr-10-0018
发表时间：
2010-09
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Dasgupta S;Koch R;Westra WH;Califano JA;Ha PK;Sidransky D;Koch WM
通讯作者：
Koch WM
影响因子：
9
作者：
Cook, C. C.;Kim, A.;Higuchi, M.
通讯作者：
Higuchi, M.