mitoXplorer 3.0, a web tool for exploring mitochondrial dynamics in single-cell RNA-seq data.

Abstract

Mitochondria are important eukaryotic organelles, best known for their function in ATP production and in cellular metabolism and signalling. It is widely accepted that their structure, composition and function differ across cell types. However, little is known about mitochondrial variability within the same cell type. To truly understand mitochondrial function and dynamics, we need to study individual cell types, as well as mitochondrial variability on a single-cell level. Based on our mitoXplorer 2.0 web tool, we introduce mitoXplorer 3.0 with new features adapted for analysing single-cell sequencing data, focusing only on mitochondria. We provide a formatting script, scXplorer to generate mitoXplorer 3.0 compatible files for upload. This script creates pseudo-bulk transcriptomes of cell types from scRNA-seq data for differential expression analysis and subsequent mitochondria-centric analysis with mitoXplorer classical interfaces. It also creates a single-cell expression matrix only containing mitochondria-associated genes (mito-genes), which can be analysed for cell-to-cell variability with novel, interactive interfaces created for mitoXplorer 3.0: these new interfaces help to identify sub-clusters of cell types based only on mito-genes and offer in-depth mitochondria-centric analysis of subpopulations. We demonstrate the usability and predictive power of mitoXplorer 3.0 using single-cell transcriptome data from a single-cell study of Spinocerebellar Ataxia Type 1. We identified several mito-processes and mito-genes that are majorly affected in SCA1 Purkinje cells and which might contribute to our understanding of mitochondrial decline and subsequent Purkinje cell loss in this disease. MitoXplorer 3.0 is freely available at https://mitoxplorer3.ibdm.univ-amu.fr.