FIGURE 2

FIGURE 2

Schematic overview of the predicted molecular machineries and D. rerio proteins localized at the membranes of peroxisomes in zebrafish. See text for further details. Matrix protein import: after synthesis on free ribosomes, cargo proteins containing the peroxisomal targeting signals PTS1 or PTS2 bind to the corresponding cytosolic receptors Pex5 (E7FGF7) or Pex7 (A8KBW8) (Pex-proteins are indicated as sole numbers) and form receptor–cargo complexes. The Pex7–cargo complex requires accessory factors for import (e.g., Pex5L, a long isoform of Pex5). Import is achieved by a complex set of integral or peripheral PMPs that form the matrix protein import machinery, which mediates docking of the cargo-bound import receptor at the peroxisomal membrane [Pex13 (Q6PFQ3), Pex14 (A0A2R8QMZ2)], cargo translocation into the matrix of the organelle by a dynamic translocon [Pex2 (E7F4V8), Pex10 (Q5XJ92), Pex12 (B0R157)], and export of the receptor back to the cytosol [Pex1 (A0A0R4IPF0), Pex6 (F1QMB0)]. Recycling of the receptor involves its ubiquitination (Ub) and extraction from the membrane by an AAA–ATPase complex (Pex1, Pex6). Pex6 binds to the membrane protein Pex26 (F1RBL0). Membrane assembly and insertion of PMPs (containing an mPTS) depend on Pex19 (F1R313), Pex3 (Q5RIV3), and Pex16 (F1RDG2). Pex19 functions as a cycling receptor/chaperone, which binds the PMPs in the cytosol and interacts with Pex3 at the peroxisomal membrane. Proliferation, growth and division: Pex11α (A3QJY9), Pex11β (Q0P453), and Pex11γ (Q4V8Z0) are involved in the regulation of peroxisome size and number (proliferation). Pex11β remodels the peroxisomal membrane and interacts with the membrane adaptors Mff (F1Q877; A8E7S0) and Fis1 (A0A2R8Q8G0), which recruit the dynamin 1-like fission GTPase Dnm1l to peroxisomes, which in mammals is activated by Pex11β. Motility: mammalian peroxisomes move along microtubules, and Miro/Rhot (Rhot1a, Q6NVC5; Rhot1b, A0A0R4IGX0; Rhot2, Q32LU1) serves as membrane adaptor for the microtubule-dependent motor proteins kinesin and dynein. Tethering: Acbd5 (E9QCH6; A5WV69) and Acbd4 (F1QA31) interact with ER-resident Vap (Vapb, Q6P2B0) to mediate peroxisome–ER contacts. Metabolite transport: uptake of fatty acids in D. rerio peroxisomes is mediated by ABC transporter proteins (Abcd1, F1RBC8; Abcd2, E7F973; Abcd3a, A0A0R4IRL4; Abcd3b, B0UY91). Other peroxisomal transporter and membrane proteins in zebrafish include (functions are in part unclear): PMP34 (Slc25a17) (A5D6T2), a peroxisomal CoA transporter; PMP52 (Tmem135) (A4QN71) and PMP24 (Pxmp4) (A0A2R8QFW3) belong to the Tim17 family of transporters; PMP22 (Pxmp2) (Q66HU7); Slc27a2/4 (F1QQC5, Q1ECW0; Q567D7), acyl-CoA synthetase long chain family member; Marc (A0A2R8PWS6), mitochondrial amidoxime reducing component; Atad1 (A0A2R8RM20, B2GP29), ATPase family AAA (ATPase associated with various cellular activities) domain-containing protein 1 with a potential role in dislocation/quality control of tail-anchored membrane proteins; Aldh3a2 (A0A2R8PW97, E9QH31), fatty aldehyde dehydrogenase; Far1/2 (A0A0R4ICF6/Q1L8Q4), fatty acyl-CoA reductase 1/2 (ether lipid biosynthesis); Mavs (F1REK4), mitochondrial antiviral signalling protein with a putative role in innate immune response; Trim37 (E7FBZ8), tripartite motif-containing protein 37, an E3 ubiquitin-protein ligase involved in Pex5 mediated peroxisomal matrix protein import; Usp30 (A2BGT0), ubiquitin-specific protease 30, a deubiquitinase involved in the turnover of peroxisomes; Pnpla8 (F1RE62), Patatin-like phospholipase domain-containing 8. Proteins with a potential dual localization to both peroxisomes and mitochondria are marked with an asterisk. Pex, peroxin; PMP, peroxisomal membrane protein (adapted from Islinger et al., 2018, but containing the zebrafish specific nomenclature).