Monzel Anna S, Devine Jack, Kapri Darshana, Enriquez Jose Antonio, Trumpff Caroline, Picard Martin
Division of Behavioral Medicine, Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA.
Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.
bioRxiv. 2025 Feb 8:2025.02.03.635951. doi: 10.1101/2025.02.03.635951.
Mitochondria are a diverse family of organelles that specialize to accomplish complimentary functions. All mitochondria share general features, but not all mitochondria are created equal. Here we develop a quantitative pipeline to define the degree of molecular specialization among different mitochondrial phenotypes - or . By distilling hundreds of validated mitochondrial genes/proteins into 149 biologically interpretable MitoPathway scores (MitoCarta 3.0) the simple mitotyping pipeline allows investigators to quantify and interpret mitochondrial diversity and plasticity from transcriptomics or proteomics data across a variety of natural and experimental contexts. We show that mouse and human multi-organ mitotypes segregate along two main axes of mitochondrial specialization, contrasting anabolic (liver) and catabolic (brain) tissues. In cultured primary human fibroblasts exhibiting robust time-dependent and treatment-induced metabolic plasticity, we demonstrate how the mitotype of a given cell type recalibrates i) over time in parallel with hallmarks of aging, and ii) in response to genetic, pharmacological, and metabolic perturbations. Investigators can now use MitotypeExplorer.org and the associated code to visualize, quantify and interpret the multivariate space of mitochondrial biology.
线粒体是一个多样化的细胞器家族，专门执行互补功能。所有线粒体都具有一般特征，但并非所有线粒体都是相同的。在这里，我们开发了一种定量方法来定义不同线粒体表型之间的分子特化程度——或者说。通过将数百个经过验证的线粒体基因/蛋白质提炼为149个具有生物学可解释性的线粒体途径得分（MitoCarta 3.0），这个简单的线粒体分型方法使研究人员能够从各种自然和实验背景下的转录组学或蛋白质组学数据中量化和解释线粒体的多样性和可塑性。我们表明，小鼠和人类多器官线粒体类型沿着线粒体特化的两个主要轴分离，这与合成代谢（肝脏）和分解代谢（大脑）组织形成对比。在表现出强大的时间依赖性和治疗诱导的代谢可塑性的原代人类成纤维细胞培养物中，我们展示了给定细胞类型的线粒体类型如何重新校准：i）随着时间的推移与衰老特征并行，以及ii）响应遗传、药理学和代谢扰动。研究人员现在可以使用MitotypeExplorer.org和相关代码来可视化、量化和解释线粒体生物学的多变量空间。
