Effects of Liposome and Cardiolipin on Folding and Function of Mitochondrial Erv1.

Xiaofan Tang,Lynda K Harris,Hui Lu

doi:10.3390/ijms21249402

Abstract

Erv1 (EC number 1.8.3.2) is an essential mitochondrial enzyme catalyzing protein import and oxidative folding in the mitochondrial intermembrane space. Erv1 has both oxidase and cytochrome c reductase activities. While both Erv1 and cytochrome c were reported to be membrane associated in mitochondria, it is unknown how the mitochondrial membrane environment may affect the function of Erv1. Here, in this study, we used liposomes to mimic the mitochondrial membrane and investigated the effect of liposomes and cardiolipin on the folding and function of yeast Erv1. Enzyme kinetics of both the oxidase and cytochrome c reductase activity of Erv1 were studied using oxygen consumption analysis and spectroscopic methods. Our results showed that the presence of liposomes has mild impacts on Erv1 oxidase activity, but significantly inhibited the catalytic efficiency of Erv1 cytochrome c reductase activity in a cardiolipin-dependent manner. Taken together, the results of this study provide important insights into the function of Erv1 in the mitochondria, suggesting that molecular oxygen is a better substrate than cytochrome c for Erv1 in the yeast mitochondria.

Highlights

Mitochondria are important organelles in eukaryotic cells, which produce most of the energy for biological processes
We investigated how liposomes and cardiolipin affect the oxidase and cytochrome c reductase activities of mitochondrial Erv1
It was reported that about 50% Erv1 was peripherally associated with the mitochondrial inner membrane (IM) [31]

Summary

Introduction

Mitochondria are important organelles in eukaryotic cells, which produce most of the energy for biological processes. Protein import and oxidative folding, conjugated with disulphide bond formation, is a unique protein import mechanism in the mitochondria intermembrane space (IMS), which is executed by the mitochondrial import and assembly (MIA) pathway [2,3,4,5]. Erv (essential for respiration and viability) [1] in yeast, or called ALR (augmenter of liver regeneration) in mammals, is an essential component of the MIA pathway, which works together with Mia to catalyze the oxidative folding of the newly imported substrate proteins in the IMS [6,7,8]. Mia acts as an oxidoreductase, interacting with the substrate proteins and transferring disulphide bonds to the substrates. A FAD-binding protein, serves as a disulphide bond generator to reoxidize the reduced Mia.

Methods

Results

Conclusion