Mitochondrial Bioenergetic and Proteomic Phenotyping Reveals Organ-Specific Consequences of Chronic Kidney Disease in Mice.
Mitochondrial Bioenergetic and Proteomic Phenotyping Reveals Organ-Specific Consequences of Chronic Kidney Disease in Mice.
复制标题
DOI：
10.3390/cells10123282
复制
发表时间：
2021-11-24
期刊：
影响因子：
6
通讯作者：
Ryan TE
中科院分区：
文献类型：
--
作者：
Thome T;Coleman MD;Ryan TE
慢性肾脏病 (CKD) 会导致肾功能下降、尿毒症和尿毒症代谢物积累。线粒体改变被认为在各种组织内的疾病病理学中发挥作用。本研究的目的是对 CKD 小鼠骨骼肌 (SkM)、心肌 (CM) 和肾组织的线粒体进行全面的生物能和蛋白质组表型分析。 5 个月大的 C57BL/6J 雄性小鼠被喂食酪蛋白对照或补充腺嘌呤的饮食 6 个月。 CKD通过血尿素氮确诊。采用线粒体诊断工作流程来检查呼吸功能、膜和氧化还原电位、活性氧的产生以及基质脱氢酶和电子传递系统 (ETS) 蛋白复合物的最大活性。此外，还进行串联质量标签辅助蛋白质组分析，以揭示线粒体蛋白质丰度可能存在的差异。当根据生理相关细胞能量需求 (ΔGATP) 进行评估时，CKD 对 SkM、CM 和肾线粒体中的线粒体能量转导产生负面影响（所有 p < 0.05），并揭示了 CKD 对线粒体健康的组织特异性影响。蛋白质组学分析表明 CM 和肾线粒体丰度发生显着变化（115 和 164 种蛋白质，p < 0.05），但 SkM 没有差异。总而言之，这些发现揭示了慢性肾功能不全对线粒体健康的组织特异性影响。
Chronic kidney disease (CKD) results in reduced kidney function, uremia, and accumulation of uremic metabolites. Mitochondrial alterations have been suggested to play a role in the disease pathology within various tissues. The purpose of this study was to perform a comprehensive bioenergetic and proteomic phenotyping of mitochondria from skeletal muscle (SkM), cardiac muscle (CM), and renal tissue from mice with CKD. The 5-month-old C57BL/6J male mice were fed a casein control or adenine-supplemented diet for 6 months. CKD was confirmed by blood urea nitrogen. A mitochondrial diagnostic workflow was employed to examine respiratory function, membrane and redox potential, reactive oxygen species production, and maximal activities of matrix dehydrogenases and electron transport system (ETS) protein complexes. Additionally, tandem-mass-tag-assisted proteomic analyses were performed to uncover possible differences in mitochondrial protein abundance. CKD negatively impacted mitochondrial energy transduction (all p < 0.05) in SkM, CM, and renal mitochondria, when assessed at physiologically relevant cellular energy demands (ΔGATP) and revealed the tissue-specific impact of CKD on mitochondrial health. Proteomic analyses indicated significant abundance changes in CM and renal mitochondria (115 and 164 proteins, p < 0.05), but no differences in SkM. Taken together, these findings reveal the tissue-specific impact of chronic renal insufficiency on mitochondrial health.
登录
查看更多内容
影响因子：
4.6
作者：
Berru, Fabian N.;Gray, Sarah E.;Ryan, Terence E.
通讯作者：
Ryan, Terence E.
DOI：
10.1002/jcsm.12202
发表时间：
2017-10
期刊：
Journal of cachexia, sarcopenia and muscle
影响因子：
--
作者：
Enoki Y;Watanabe H;Arake R;Fujimura R;Ishiodori K;Imafuku T;Nishida K;Sugimoto R;Nagao S;Miyamura S;Ishima Y;Tanaka M;Matsushita K;Komaba H;Fukagawa M;Otagiri M;Maruyama T
通讯作者：
Maruyama T
影响因子：
8.8
作者：
Fisher-Wellman KH;Davidson MT;Narowski TM;Lin CT;Koves TR;Muoio DM
通讯作者：
Muoio DM
影响因子：
20.1
作者：
Davidson, Michael T.;Grimsrud, Paul A.;Lai, Ling;Draper, James A.;Fisher-Wellman, Kelsey H.;Narowski, Tara M.;Abraham, Dennis M.;Koves, Timothy R.;Kelly, Daniel P.;Muoio, Deborah M.
通讯作者：
Muoio, Deborah M.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y