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The life cycle of the peroxisome

Nature Reviews Molecular Cell Biology volume 2, pages 357–368 (2001)Cite this article

Key Points

  • Like the Golgi apparatus, the population of peroxisomes in a cell consists of structurally and functionally distinct subcompartments (subforms) that are related through the ordered conversion of one subform to another.

  • The import of a limited subset of peroxisomal membrane proteins commits a specialized preperoxisomal endomembrane to become the earliest peroxisomal precursor (nascent peroxisome). Nascent peroxisomes can import another subset of membrane proteins and the bulk of matrix proteins, and they eventually mature into functional peroxisomes in a multistep process. In yeast and plant cells, the endoplasmic reticulum, might serve as the preperoxisomal endomembrane. The nature of the preperoxisomal endomembrane is under debate. In human cells, a preperoxisomal endomembrane might exist as an autonomous vesicular structure.

  • Many soluble and membrane-associated components of the peroxisomal machineries specific for the import of membrane and matrix proteins have been identified. These import machineries probably assemble in a temporally and spatially ordered manner in distinct intermediates along the peroxisome assembly pathway.

  • Whereas only unfolded, monomeric proteins can be translocated across the endoplasmic reticulum and mitochondrial membranes, the machinery for the import of matrix proteins can translocate completely folded polypeptides and oligomeric proteins across the peroxisomal membrane.

  • Peroxisomes undergo both constitutive (independent of extracellular stimuli) division during mitosis and regulated division induced in response to some external signal. A specific subset of peroxins coordinates the growth and regulated division of peroxisomes.

Abstract

Peroxisomes are highly adaptable organelles that carry out oxidative reactions. Distinct cellular machineries act together to coordinate peroxisome formation, growth, division, inheritance, turnover, movement and function. Soluble and membrane-associated components of these machineries form complex networks of physical and functional interactions that provide supramolecular control of the precise dynamics of peroxisome biogenesis.

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Figure 1: Appearance of peroxisomes in different organisms.
Figure 2: Import of peroxisomal membrane proteins.
Figure 3: Import of matrix proteins into peroxisomes.
Figure 4: Two models for the dynamics of multistep peroxisome assembly.
Figure 5: Two models for the formation of early peroxisomal precursors.

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Acknowledgements

We would like to thank N.-H. Chua, I. Coppens, G. Jedd and F.R. Opperdoes for providing images for Fig. 1 and for helpful discussion. This work was supported by grants from the Canadian Institutes of Health Research (CIHR) to R.A.R. R.A.R. is a Senior Scientist of the CIHR and an International Research Scholar of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Department of Cell Biology, University of Alberta, Edmonton, T6G 2H7, Alberta, Canada

    Vladimir I. Titorenko & Richard A. Rachubinski

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  1. Vladimir I. Titorenko
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DATABASE LINKS

catalase

peroxisome biogenesis disorders

PMP22

TriC

Pex19

Pex11

Pex14

PMP70

Pex16

Hsp40

Hsp70

Djp1

Hsp90

Hsp73

Pex5

Pex7

carnitine acetyltransferase

acyl-CoA oxidase

Pex12

Pex1

Pex6

Pex18

Pex21

Pex4

ARF1

COPI

PMP47

acyl-CoA oxidase

fatty acyl-CoA synthetase

FURTHER INFORMATION

Rachubinski lab

The peroxisome website

Subramani lab

ENCYCLOPEDIA OF LIFE SCIENCES

Protein import into peroxisomes

Peroxisomes: methods for preparation

Plant cells: peroxisomes and glyoxysomes

Glossary

PEROXINS

Proteins required for various aspects of peroxisome (microbody) biogenesis, including assembly of the peroxisomal membrane, import of peroxisomal matrix proteins, peroxisome proliferation and peroxisome inheritance.

mPTS1

Peroxisomal membrane targeting signal 1 for post-translational targeting of peroxisomal membrane proteins directly from the cytosol. There is no clear sequence consensus for the mPTS1, but several motifs have been reported, including (K/R)(K/R)X3–7(T/S)X2(D/E) and (Y)X3(L)X3(P)X3(K/Q/N).

mPTS2

Peroxisomal membrane targeting signal 2 for targeting of peroxisomal membrane proteins indirectly from the endoplasmic reticulum (ER). The mPTS2 acts in the ER lumen. Two similar consensus motifs have been reported, namely (R/K)X(K/R)X (K/R)X(L/I)X9–10(F/Y) and (L/I/V)X(R)X(K/R)X(K)X(L/I)

PTS1

Carboxy-terminal peroxisomal targeting signal 1 found in most peroxisomal matrix proteins. It is a tripeptide with the consensus motif (S/A/C)(K/R/H)(L/M/I).

PTS2

Peroxisomal targeting signal 2 that has been found so far at the amino termini of four peroxisomal matrix proteins. It is a nonapeptide with the consensus motif (R/K)(L/V/I)X5(H/Q)(L/A).

CHAPERONE

Protein that mediates assembly of another polypeptide-containing structure, but does not form part of the completed structure, or participate in its biological function.

PREPEROXISOMAL ENDOMEMBRANE

An endomembrane committed to become the earliest peroxisomal precursor (the nascent peroxisome), and not another organelle, by uptake of a limited subset of peroxisomal membrane proteins. Also called early preperoxisome.

NASCENT PEROXISOME

The earliest peroxisomal precursor formed by uptake of a limited subset of peroxisomal membrane proteins into a preperoxisomal endomembrane and that can import an additional set of membrane proteins to become an early peroxisomal precursor. Also called late preperoxisome.

HSP

(Heat-shock protein). Protein induced in response to elevated temperature, classified according to its size. Functions as a molecular chaperone.

TPR

The tetratricopeptide repeat motif consists of a highly degenerate 34-amino-acid repeat believed to form an interlocking series of α-helices. The TPR is thought to mediate protein–protein interactions, preferably with proteins that have WD-40 repeats.

WD-40

Repeat of ∼40 amino acids with a characteristic central Trp–Asp motif. WD-40 proteins are often associated with TPR- repeat proteins.

RING

A cysteine-rich 'RING' finger domain of 40 to 60 amino acids, also called the C3HC4 Zn finger, which binds two atoms of Zn and might mediate protein–protein interactions. Most RING-finger proteins have been shown to bind DNA.

AAA ATPASES

ATPases associated with different cellular activities that contain one or two AAA motifs of 230 to 250 amino acids, including the Walker homology sequences of P-loop ATPases and regions of similarity unique to AAA proteins.

SH3

60-amino-acid Src homology 3 domain that mediates the assembly of specific protein complexes through binding to proline-rich peptides.

MATURE PEROXISOMES

Metabolically active, functional peroxisomes that contain the complete complement of membrane and matrix proteins and membrane lipids.

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Titorenko, V., Rachubinski, R. The life cycle of the peroxisome. Nat Rev Mol Cell Biol 2, 357–368 (2001). https://doi.org/10.1038/35073063

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