Peroxisomal ATP Uptake Is Provided by Two Adenine Nucleotide Transporters and the ABCD Transporters.

Carlo W T Van Roermund,Ronald J A Wanders,Hans R Waterham,Nicole Linka,Lodewijk Ijlst

doi:10.3389/fcell.2021.788921

Abstract

Peroxisomes are essential organelles involved in various metabolic processes, including fatty acid β-oxidation. Their metabolic functions require a controlled exchange of metabolites and co-factors, including ATP, across the peroxisomal membrane. We investigated which proteins are involved in the peroxisomal uptake of ATP in the yeast Saccharomyces cerevisiae. Using wild-type and targeted deletion strains, we measured ATP-dependent peroxisomal octanoate β-oxidation, intra-peroxisomal ATP levels employing peroxisome-targeted ATP-sensing reporter proteins, and ATP uptake in proteoliposomes prepared from purified peroxisomes. We show that intra-peroxisomal ATP levels are maintained by different peroxisomal membrane proteins each with different modes of action: 1) the previously reported Ant1p protein, which catalyzes the exchange of ATP for AMP or ADP, 2) the ABC transporter protein complex Pxa1p/Pxa2p, which mediates both uni-directional acyl-CoA and ATP uptake, and 3) the mitochondrial Aac2p protein, which catalyzes ATP/ADP exchange and has a dual localization in both mitochondria and peroxisomes. Our results provide compelling evidence for a complementary system for the uptake of ATP in peroxisomes.

Highlights

Peroxisomes are single-membrane bounded organelles found in cells of all eukaryotic species
In addition to Ant1p, these include the ABC transporter protein complex Pxa1p/Pxa2p, which catalyzes peroxisomal ATP uptake as well as acyl-CoA import, and the mitochondrial carrier family (MCF) carrier Aac2p, a predominantly mitochondrial protein, which we found partially localized to peroxisomes and which catalyzes the exchange of cytosolic ATP for peroxisomal ADP
Earlier work showed that the peroxisomal membrane protein Ant1p functions as an antiporter of ATP against AMP or ADP and most probably is responsible for the peroxisomal uptake of ATP required for the intra-peroxisomal activation of fatty acids (Palmieri et al, 2001; van Roermund et al, 2001)

Summary

Introduction

Peroxisomes are single-membrane bounded organelles found in cells of all eukaryotic species. They can be involved in a large variety of metabolic pathways which may differ per species but always includes the degradation of fatty acids through β-oxidation. In mammals, including humans, peroxisomes play an important role in ether phospholipid biosynthesis, fatty acid alphaoxidation, bile acid synthesis, glyoxylate detoxification and H2O2 degradation (Wanders and Waterham, 2006; Van Veldhoven, 2010). Peroxisomes only catalyze a specific subset of enzyme reactions with other reactions catalyzed in the cytosol, mitochondria and/or endoplasmic reticulum (Wanders, 2014). The involvement of different cellular compartments implies that the various metabolites involved, i.e

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