#peroxisome

Protein Sorting and Trafficking

What is the primary function of Pex11 in peroxisomes?

Peroxisomes are single membrane organelles handling beta oxidation of very long chain fatty acids, alpha oxidation, plasmalogen synthesis and H2O2 detoxification via catalase. Their abundance adapts to metabolic demand through fission of preexisting organelles rather than solely de novo budding from ER. Pex11 family proteins, including Pex11 alpha beta gamma isoforms in mammals, are conserved peroxisomal membrane proteins enriched in regions of high curvature. Upon induction by oleate, fibrates via PPAR alpha, or cold, PEX11 genes transcribed, proteins oligomerize through amphipathic helices a

Ref: Lodish et al., Molecular Cell Biology, 9th ed., Chapter 13: Peroxisome Biogenesis and Pex11 Division.

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Protein Sorting and Trafficking

Which protein is required for peroxisomal membrane biogenesis?

De novo biogenesis and growth peroxisomal membrane depends targeted insertion peroxisomal membrane proteins PMPs specialized machinery distinct matrix pathway. PMPs including docking Pex14 Pex13 fission factors Pex11 isoforms transporters ABCD1-3 synthesized free cytosolic ribosomes containing hydrophobic transmembrane domains aggregation prone requiring chaperoning. Cytosolic receptor chaperone Pex19 farnesylated C-terminal CAAX box binds PMPs hydrophobic groove preventing aggregation maintaining solubility delivering peroxisomal membrane docking platform. Targeting essential factors Pex3 42

Ref: Distel et al., Annu Rev Biochem: Pex3 and Pex16 essential for peroxisomal membrane biogenesis.

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Protein Sorting and Trafficking

What happens when Pex5 is ubiquitinated by Pex2, Pex10, and Pex12?

Import receptor recycling distinguishes peroxisomes mitochondria requiring extraction shuttling receptor after cargo delivery. After releasing matrix cargo lumen transient pore Pex5 remains embedded peroxisomal membrane peripherally N-terminus facing cytosol partial retrotranslocation. Return cytosol new cycles membrane extraction requires ubiquitination generating handle AAA motor. Specialized peroxisomal E3 ligase complex RING proteins Pex2 Pex10 Pex12 heterotrimeric zinc coordinated embedded membrane associates cytosolic E2 Pex4 anchored membrane Pex22. Pex5 undergoes thioester monoubiquiti

Ref: Platta et al., Cell Cycle 2007: Pex5 monoubiquitination by Pex2/10/12 recycles receptor via Pex1/6.

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Protein Sorting and Trafficking

Which receptor recognizes peroxisomal proteins containing a PTS1 signal?

Peroxisomal biogenesis uses two soluble receptors distinguishing two signals. Pex5 70 kDa primary receptor PTS1 pathway handling bulk matrix proteins catalase ACOX1 DBP. Structurally N-terminal half intrinsically disordered contains multiple WXXXF motifs interacting peroxisomal membrane docking protein Pex14 N-terminal domain plus cysteine ubiquitination sites recycling amphipathic helices; C-terminal seven tetratricopeptide repeats TPR 34 aa folding two half-rings superhelical clamp central cavity accommodating C-terminal tripeptide Ser-Lys-Leu water-mediated hydrogen bonds explaining toleran

Ref: Smith & Subramani, Annu Rev Cell Dev Biol 2019: Pex5 receptor recognizes PTS1 signal.

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Protein Sorting and Trafficking

What type of targeting sequence do peroxisomal matrix proteins contain?

Peroxisomes single-membrane oxidative organelles ubiquitous eukaryotes performing fatty acid alpha beta-oxidation very long chain branched chain detoxifying hydrogen peroxide catalase plasmalogen ether lipid synthesis. Matrix content exceeding 50 enzymes imported post-translationally cytosol free ribosomes. Majority around 90 percent carry peroxisomal targeting signal type 1 PTS1 extreme C-terminus tripeptide (S/A/C)-(K/R/H)-(L/M) canonical most efficient Ser-Lys-Leu derived firefly luciferase discovery. Additional upstream residues modulate affinity receptor. PTS1 recognized tetratricopeptide

Ref: Lodish et al., MCB: PTS1 SKL tripeptide targets matrix proteins to peroxisomes.

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