Myristoyl group-aided protein import into the mitochondrial intermembrane space

Eri Ueda,Chika Kakuta,Haruka Sakaue,Shin Kawano,Toshiya Endo,Shunsuke Matsumoto,Yasushi Tamura

doi:10.1038/s41598-018-38016-1

Eri Ueda, Chika Kakuta + Show 5 more

Open Access

https://doi.org/10.1038/s41598-018-38016-1

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Abstract

The MICOS complex mediates formation of the crista junctions in mitochondria. Here we analyzed the mitochondrial import pathways for the six yeast MICOS subunits as a step toward understanding of the assembly mechanisms of the MICOS complex. Mic10, Mic12, Mic26, Mic27, and Mic60 used the presequence pathway to reach the intermembrane space (IMS). In contrast, Mic19 took the TIM40/MIA pathway, through its CHCH domain, to reach the IMS. Unlike canonical TIM40/MIA substrates, presence of the N-terminal unfolded DUF domain impaired the import efficiency of Mic19, yet N-terminal myristoylation of Mic19 circumvented this effect. The myristoyl group of Mic19 binds to Tom20 of the TOM complex as well as the outer membrane, which may lead to “entropy pushing” of the DUF domain followed by the CHCH domain of Mic19 into the import channel, thereby achieving efficient import.

Highlights

The mitochondrial cristae organizing system (MICOS) complex mediates formation of the crista junctions in mitochondria
TOM complex as well as the outer membrane, which may lead to “entropy pushing” of the DUF domain followed by the CHCH domain of Mic[19] into the import channel, thereby achieving efficient import
Mitochondria consist of two membranes, the outer membrane (OM) and inner membrane (IM), and two aqueous compartments, the intermembrane space (IMS) and matrix

Summary

Introduction

The MICOS complex mediates formation of the crista junctions in mitochondria. Cristae are tubular or lamellar membrane invaginations of the IM, which are connected to the IBM by narrow constrictions called crista junctions (CJs)[3]. CJs are narrow constrictions that connect the IMS with the intracrista space, but probably pose a diffusion barrier for metabolites, soluble proteins and membrane proteins between the IMS plus IBM and the intracrista space plus crista membrane[6,7,8]. Cristae formation requires dimerization of the F1Fo-ATP synthase, which generates a significant curvature of the IM for forming a tip of the cristae[9,10], and the presence of the mitochondrial cristae organizing system (MICOS) complex, which mediates formation of the CJs with a negative curvature and contacts between the IM and OM11–14.

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