Fig. 1

Pathway-related genes in peroxisomes and mitochondria. For simplicity, only human gene symbols are shown within the figure. a Mammalian peroxisome biogenesis factors include matrix protein receptors PEX5 and PEX7, membrane biogenesis factors PEX3, PEX16, and PEX19; docking and import complex components PEX13 and PEX14; E3 ubiquitin ligase complex PEX2, PEX10, and PEX12; the AAA complex PEX1 and PEX6 with tail-anchored PEX26. TYSND1 and LONP2 process imported matrix proteins. The PEX11 family is involved in the elongation of peroxisomes; the fission of peroxisomes and mitochondria requires FIS1, MFF, DNM1L, and GDAP1. E3 ubiquitin ligase TRIM37 and autophagy receptors NBR1 and SQSTM1 mediate pexophagy. b Metabolite flux in peroxisomes relies on pore formation by PXMP2, PXMP4, and SLC25A17. ABCD1, ABCD2, and ABCD3 import FAs with different substrate selectivity. c CAT, EPHX2, and GSTK1 facilitate ROS metabolism, and D-AAs are oxidized by DAO and DDO. d BCFAs are metabolized by PHYH, HACL1, and ALDH3A2. SLC27A2 activates and transports BCFAs. AMACR converts the (2R)-enantiomer. e Mitochondrial β-oxidation requires FA import by the carnitine shuttle CPT1A, CPT1B, CPT1C, CPT2, and SLC25A20 (red), see b for peroxisomal import factors. Mitochondrial import is followed by dehydrogenation (blue) by ACADS, ACADSB, ACADM, ACADL, ACADVL, ACAD9, or ACAD10; the peroxisomal analogs are ACOX1, ACOX2, and ACOX3. Mitochondrial ECI1 and DECR1 break down unsaturated FAs by isomerization and oxidation of double bonds. Hydration, oxidation, and thiolytic cleavage are carried out by multifunctional or individual enzymes (green): HADHA, HADHB, ECHS1, HADH, ACAA2 in mitochondria, and EHHADH, HSDB174, ACAA1 in peroxisomes. ACOT4 and ACOT8 catalyze the hydrolysis of acyl-CoAs into free FAs and CoA. CROT catalyzes the export of peroxisomal FAs. ACBD4 and ACBD5 tether peroxisomes to the ER. f Plasmalogen synthesis involves FAR1- or FAR2-mediated reduction of acyl-CoAs to primary fatty alcohols and synthesis of an ether-linked intermediate by GNPAT and AGPS. The peroxisomal enzymes, BAAT and ECI2 are essential for BA and PUFA synthesis, respectively