Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Sequence Features of Mitochondrial Transporter Protein Families

Version 1 : Received: 20 October 2020 / Approved: 23 October 2020 / Online: 23 October 2020 (11:00:09 CEST)

A peer-reviewed article of this Preprint also exists.

Gyimesi, G.; Hediger, M.A. Sequence Features of Mitochondrial Transporter Protein Families. Biomolecules 2020, 10, 1611. Gyimesi, G.; Hediger, M.A. Sequence Features of Mitochondrial Transporter Protein Families. Biomolecules 2020, 10, 1611.


Mitochondrial carriers facilitate the transfer of small molecules across the inner mitochondrial membrane (IMM) to support mitochondrial function and core cellular processes. In addition to the classical mitochondrial carrier family SLC25, the past decade led to the discovery of additional protein families that exhibit IMM localization and transporter-like properties. These include mitochondrial pyruvate carriers, sideroflexins and mitochondrial cation/H+ exchangers that have been linked to vital physiological functions and disease. Their structures and transport mechanisms are still largely unknown and understudied. Protein sequence analysis per se can often pinpoint hotspots that are of functional or structural importance. In this review, we summarize current knowledge about sequence features of mitochondrial transporters with a special focus on the newly included SLC54, SLC55 and SLC56 families of the SLC solute carrier superfamily. Taking a step further, we combined sequence conservation analysis with transmembrane segment and secondary structure prediction methods to extract residue positions and sequence motifs that likely play a role in substrate binding, binding site gating or structural stability. We hope that our review will help guide future experimental efforts by the scientific community to unravel the transport mechanism and structure of these novel mitochondrial carriers.


mitochondrial carriers; SLC transporters; SLC25; MCF; SLC54; MPC; SLC55; LETM; SLC56; sideroflexin; ABC transporter; sequence analysis; protein targeting


Biology and Life Sciences, Biochemistry and Molecular Biology

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