TY - JOUR
T1 - Peroxisomal Metabolite and Cofactor Transport in Humans
AU - Chornyi, Serhii
AU - IJlst, Lodewijk
AU - van Roermund, Carlo W. T.
AU - Wanders, Ronald J. A.
AU - Waterham, Hans R.
N1 - Funding Information: Partial localization of MCT1 and MCT2 in rat liver peroxisomes was initially reported by McClelland et al. (2003). This localization supported the hypothesis of a peroxisomal lactate shuttle involved in the peroxisomal exchange of lactate and pyruvate that would be required for the reoxidation of NADH, produced by peroxisomal beta-oxidation (see also “Shuttle Systems”). This hypothesis was supported by the stimulation of palmitoyl-CoA beta-oxidation of purified peroxisomes upon pyruvate supplementation. Also, an inhibitor of MCT proteins, α-cyano-4-hydroxycinnamate, was able to partly inhibit this stimulation (McClelland et al., 2003). Publisher Copyright: © Copyright © 2021 Chornyi, IJlst, van Roermund, Wanders and Waterham.
PY - 2021/1/11
Y1 - 2021/1/11
N2 - Peroxisomes are membrane-bound organelles involved in many metabolic pathways and essential for human health. They harbor a large number of enzymes involved in the different pathways, thus requiring transport of substrates, products and cofactors involved across the peroxisomal membrane. Although much progress has been made in understanding the permeability properties of peroxisomes, there are still important gaps in our knowledge about the peroxisomal transport of metabolites and cofactors. In this review, we discuss the different modes of transport of metabolites and essential cofactors, including CoA, NAD+, NADP+, FAD, FMN, ATP, heme, pyridoxal phosphate, and thiamine pyrophosphate across the peroxisomal membrane. This transport can be mediated by non-selective pore-forming proteins, selective transport proteins, membrane contact sites between organelles, and co-import of cofactors with proteins. We also discuss modes of transport mediated by shuttle systems described for NAD+/NADH and NADP+/NADPH. We mainly focus on current knowledge on human peroxisomal metabolite and cofactor transport, but also include knowledge from studies in plants, yeast, fruit fly, zebrafish, and mice, which has been exemplary in understanding peroxisomal transport mechanisms in general.
AB - Peroxisomes are membrane-bound organelles involved in many metabolic pathways and essential for human health. They harbor a large number of enzymes involved in the different pathways, thus requiring transport of substrates, products and cofactors involved across the peroxisomal membrane. Although much progress has been made in understanding the permeability properties of peroxisomes, there are still important gaps in our knowledge about the peroxisomal transport of metabolites and cofactors. In this review, we discuss the different modes of transport of metabolites and essential cofactors, including CoA, NAD+, NADP+, FAD, FMN, ATP, heme, pyridoxal phosphate, and thiamine pyrophosphate across the peroxisomal membrane. This transport can be mediated by non-selective pore-forming proteins, selective transport proteins, membrane contact sites between organelles, and co-import of cofactors with proteins. We also discuss modes of transport mediated by shuttle systems described for NAD+/NADH and NADP+/NADPH. We mainly focus on current knowledge on human peroxisomal metabolite and cofactor transport, but also include knowledge from studies in plants, yeast, fruit fly, zebrafish, and mice, which has been exemplary in understanding peroxisomal transport mechanisms in general.
KW - carrier
KW - cofactor
KW - exchanger
KW - membrane contact sites
KW - metabolism
KW - peroxisomes
KW - transporter
UR - http://www.scopus.com/inward/record.url?scp=85099803234&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fcell.2020.613892
DO - https://doi.org/10.3389/fcell.2020.613892
M3 - Review article
C2 - 33505966
SN - 2296-634X
VL - 8
JO - Frontiers in cell and developmental biology
JF - Frontiers in cell and developmental biology
M1 - 613892
ER -