Peroxisomal Cofactor Transport

Abstract

Peroxisomes are eukaryotic organelles that are essential for growth and development. They are highly metabolically active and house many biochemical reactions, including lipid metabolism and synthesis of signaling molecules. Most of these metabolic pathways are shared with other compartments, such as Endoplasmic reticulum (ER), mitochondria, and plastids. Peroxisomes, in common with all other cellular organelles are dependent on a wide range of cofactors, such as adenosine 5′-triphosphate (ATP), Coenzyme A (CoA), and nicotinamide adenine dinucleotide (NAD). The availability of the peroxisomal cofactor pool controls peroxisome function. The levels of these cofactors available for peroxisomal metabolism is determined by the balance between synthesis, import, export, binding, and degradation. Since the final steps of cofactor synthesis are thought to be located in the cytosol, cofactors must be imported into peroxisomes. This review gives an overview about our current knowledge of the permeability of the peroxisomal membrane with the focus on ATP, CoA, and NAD. Several members of the mitochondrial carrier family are located in peroxisomes, catalyzing the transfer of these organic cofactors across the peroxisomal membrane. Most of the functions of these peroxisomal cofactor transporters are known from studies in yeast, humans, and plants. Parallels and differences between the transporters in the different organisms are discussed here.

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

“…Current consensus holds that peroxisomes are equipped with two fundamentally different mechanisms for metabolite transport across their membrane, which includes 1) diffusion of small Mw metabolites (<400 Da) via channel-forming membrane proteins, and 2) carrier-mediated transport of higher Mw metabolites, such as acyl-CoAs and ATP. Genetic complementation approaches, sequence similarity searches, and proteomic analyses of highly purified peroxisomes of mouse ( Mi et al, 2007 ; Wiese et al, 2007 ), human ( Gronemeyer et al, 2013 ), plants ( Plett et al, 2020 ), and the yeast Saccharomyces cerevisiae ( Yi et al, 2002 ; Chen and Williams, 2018 ) have led to the identification of several integral peroxisomal membrane proteins which, based on (partial) sequence similarity shared with known transport proteins, may function as peroxisomal metabolite transport proteins.…”

“…Ant1p is an MCF member with strong similarity to human PMP34 but, in contrast to PMP34, demonstrated to catalyze the exchange of cytosolic ATP for peroxisomal AMP or ADP. AMP is generated upon the intra-peroxisomal ATP-dependent activation of fatty acids by the acyl-CoA synthetase Faa2p ( Palmieri et al, 2001 ; van Roermund et al, 2001 ) while ADP is generated by the peroxisomal nudix family members NPY1 and PCD1 ( Plett et al, 2020 ).…”

Role of solute carrier transporters SLC25A17 and SLC27A6 in acquired resistance to enzalutamide in castration‐resistant prostate cancer

“…36 Lauric acid, a medium-chain fatty acid, is activated in the peroxisomal matrix by Faa2p, whereas oleic acid is imported into the peroxisome as a CoA ester. 37 Fatty acid such as phytanic acid which is present in dairy products and red meat is transported by SLC25A17 into the peroxisome where it undergoes breakdown into pristanic acid, a substrate for α-Methylacyl-CoA Racemase (AMACR). 38,39 AMACR is a well-known peroxisomal enzyme that has been shown to be overexpressed in prostate cancer.…”

Peroxisomal Metabolite and Cofactor Transport in Humans

“…We will focus mainly on such proteins in humans and partly in plants, yeast, fruit fly, zebrafish, and mice. For previous reviews on peroxisomal metabolite transport we refer to Antonenkov and Hiltunen (2006 , 2012) , Visser et al (2007b) , Plett et al (2020) , and for a specialized review on peroxisomal metabolite transporter proteins in plants, we refer to an excellent review by ( Charton et al, 2019 ).…”