MTSviewer: a database to visualize mitochondrial targeting sequences, cleavage sites, and mutations on protein structures

Abstract

SummaryMitochondrial dysfunction is implicated in a wide array of human diseases ranging from neurodegenerative disorders to cardiovascular defects. The coordinated localization and import of proteins into mitochondria are essential processes that ensure mitochondrial homeostasis and consequently cell survival. The localization and import of most mitochondrial proteins are driven by N-terminal mitochondrial targeting sequences (MTSs), which interact with import machinery and are removed by the mitochondrial processing peptidase (MPP). The recent discovery of internal MTSs - those which are distributed throughout a protein and act as import regulators or secondary MPP cleavage sites - has expanded the role of both MTSs and MPP beyond conventional N-terminal regulatory pathways. Still, the global mutational landscape of MTSs remains poorly characterized, both from genetic and structural perspectives. To this end, we have integrated a variety of tools into one harmonized R/Shiny database called MTSviewer (https://neurobioinfo.github.io/MTSvieweR/) which combines MTS predictions, cleavage sites, genetic variants, pathogenicity predictions, and N-terminomics data with structural visualization using AlphaFold models of human and yeast mitochondrial proteomes. Availability and ImplementationMTSviewer is freely available on the web at https://neurobioinfo.github.io/MTSvieweR/. Source code is available at https://github.com/neurobioinfo/MTSvieweR. Contacteanfrancois.trempe@mcgill.ca; sali.farhan@mcgill.ca