Mdm10 is an ancient eukaryotic porin co-occurring with the ERMES complex

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• 作者：Nadine Flinner ; Lars Ellenrieder ; Sebastian B. Stiller ; Thomas Becker ; Enrico Schleiff ; Oliver Mirus
• 关键词：Eukaryotic 尾-barrel protein ; Multiple sequence alignment ; Homology modeling ; Phylogenetic analysis ; ERMES ; SAM
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：December, 2013
• 年：2013
• 卷：1833
• 期：12
• 页码：3314-3325
• 全文大小：1675 K

文摘

Mitochondrial 尾-barrel proteins fulfill central functions in the outer membrane like metabolite exchange catalyzed by the voltage-dependent anion channel (VDAC) and protein biogenesis by the central components of the preprotein translocase of the outer membrane (Tom40) or of the sorting and assembly machinery (Sam50). The mitochondrial division and morphology protein Mdm10 is another essential outer membrane protein with proposed 尾-barrel fold, which has so far only been found in Fungi. Mdm10 is part of the endoplasmic reticulum mitochondria encounter structure (ERMES), which tethers the ER to mitochondria and associates with the SAM complex. In here, we provide evidence that Mdm10 phylogenetically belongs to the VDAC/Tom40 superfamily. Contrary to Tom40 and VDAC, Mdm10 exposes long loops towards both sides of the membrane. Analyses of single loop deletion mutants of Mdm10 in the yeast Saccharomyces cerevisiae reveal that the loops are dispensable for Mdm10 function. Sequences similar to fungal Mdm10 can be found in species from Excavates to Fungi, but neither in Metazoa nor in plants. Strikingly, the presence of Mdm10 coincides with the appearance of the other ERMES components. Mdm10's presence in both unikonts and bikonts indicates an introduction at an early time point in eukaryotic evolution.