Mitochondrial Diagnostics: A Multiplexed Assay Platform for Comprehensive Assessment of Mitochondrial Energy Fluxes.
Mitochondrial Diagnostics: A Multiplexed Assay Platform for Comprehensive Assessment of Mitochondrial Energy Fluxes.
复制标题
DOI：
10.1016/j.celrep.2018.08.091
复制
发表时间：
2018-09-25
期刊：
影响因子：
8.8
通讯作者：
Muoio DM
中科院分区：
文献类型：
--
作者：
Fisher-Wellman KH;Davidson MT;Narowski TM;Lin CT;Koves TR;Muoio DM
慢性代谢性疾病与线粒体功能障碍的分子特征有关。然而，转录组、蛋白质组和/或代谢组的分子重塑并不一定转化为赋予生理表型的功能后果。这项工作旨在通过开发和验证一个全面评估线粒体能量转导的多重分析平台来弥合分子表型组学和功能表型组学之间的差距。该平台的诊断能力来自于肌酸激酶能量钳技术的改进版本，该技术与脱氢酶活性和ATP合成率的多重分析并行进行。总而言之，这些检测方法提供了线粒体网络的诊断覆盖率，其水平接近于分子组学技术。将该平台应用于骨骼肌和心脏线粒体的比较，揭示了对组织特定能量转移效率差异的机械洞察。这个平台为揭示线粒体生物能量学和人类疾病之间的联系提供了令人兴奋的机会。Fisher-Wellman等人。开发和验证多重分析平台，允许在模拟体内能源供需波动的条件下对线粒体生物能量学进行深入和全面的表型分析。该报告提供了构建这一平台的蓝图，以及执行和解释化验的工作流程。
Chronic metabolic diseases have been linked to molecular signatures of mitochondrial dysfunction. Nonetheless, molecular remodeling of the transcriptome, proteome, and/or metabolome does not necessarily translate to functional consequences that confer physiologic phenotypes. The work here aims to bridge the gap between molecular and functional phenomics by developing and validating a multiplexed assay platform for comprehensive assessment of mitochondrial energy transduction. The diagnostic power of the platform stems from a modified version of the creatine kinase energetic clamp technique, performed in parallel with multiplexed analyses of dehydrogenase activities and ATP synthesis rates. Together, these assays provide diagnostic coverage of the mitochondrial network at a level approaching that gained by molecular “-omics” technologies. Application of the platform to a comparison of skeletal muscle versus heart mitochondria reveals mechanistic insights into tissue-specific distinctions in energy transfer efficiency. This platform opens exciting opportunities to unravel the connection between mitochondrial bioenergetics and human disease. Fisher-Wellman et al. develop and validate a multiplexed assay platform that permits deep and comprehensive phenotyping of mitochondrial bioenergetics under conditions that model in vivo fluctuations in energy supply and demand. The report provides a blueprint for building this platform and a workflow for executing and interpreting the assays.
登录
查看更多内容
影响因子：
7.4
作者：
Gilliam, Laura A. A.;Fisher-Wellman, Kelsey H.;Lin, Chien-Te;Maples, Jill M.;Cathey, Brook L.;Neufer, P. Darrell
通讯作者：
Neufer, P. Darrell
DOI：
10.3109/10409238.2015.1031879
发表时间：
2015
影响因子：
6.5
作者：
Gonzalez Herrera KN;Lee J;Haigis MC
通讯作者：
Haigis MC
影响因子：
2.9
作者：
Glancy, Brian;Willis, Wayne T.;Balaban, Robert S.
通讯作者：
Balaban, Robert S.
影响因子：
7.4
作者：
Fisher-Wellman, Kelsey H.;Gilliam, Laura A. A.;Neufer, P. Darrell
通讯作者：
Neufer, P. Darrell
影响因子：
20.1
作者：
Carley AN;Taegtmeyer H;Lewandowski ED
通讯作者：
Lewandowski ED