Restoration of PEX2 peroxisome assembly defects by overexpression of PMP70

Jutta Gärtner, Ute Brosius, Cassandra Obie, Paul A Watkins, David Valle

Research output: Contribution to journalArticle

Abstract

The mutant Chinese hamster ovary (CHO) cell line Z78/C has defective peroxisome assembly due to a missense mutation in PEX2, the gene which encodes the 35 kDa peroxisomal integral membrane protein. In humans, PEX2 mutations are responsible for complementation group 10 of the human peroxisome biogenesis disorders (PBD), a genetically heterogeneous group of lethal, autosomal recessive diseases including the Zellweger syndrome and related phenotypes. To develop additional cellular models for Zellweger syndrome, we produced a series of new mutant CHO cell clones in the same complementation group as Z78/C (Z2, Z7, Z22, and Z105). As expected, expression of human PEX2 restores peroxisomal biogenesis in all of these clones. Surprisingly expression of the human 70 kDa peroxisomal membrane protein (PMP70) also restores peroxisome biogenesis in these same CHO cell clones. We confirmed this effect of PMP70 expression on peroxisome biogenesis by determining the subcellular latency of catalase, the immunohistochemical localization of catalase and the β-oxidation of very long chain fatty acids (VLCFA). By contrast, expression of a mutant allele of PMP70 identified in a patient with Zellweger syndrome did not restore peroxisome biogenesis in the PEX2-deficient CHO cell clones. Our results indicate that overexpression of PMP70 suppresses the phenotype of PEX2 gene mutations. These observations suggest a functional interaction between PEX2 and PMP70 in the peroxisome membrane.

Original languageEnglish (US)
Pages (from-to)237-245
Number of pages9
JournalEuropean Journal of Cell Biology
Volume76
Issue number4
StatePublished - 1998
Externally publishedYes

Fingerprint

Peroxisomes
Zellweger Syndrome
Cricetulus
Ovary
Clone Cells
Catalase
Phenotype
Mutation
Missense Mutation
Genes
Membrane Proteins
Fatty Acids
Alleles
Cell Line
Membranes

Keywords

  • Gene expression
  • Human peroxisomal membrane proteins
  • Peroxisome
  • Peroxisome assembly mutants
  • Peroxisome biogenesis disorders

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Restoration of PEX2 peroxisome assembly defects by overexpression of PMP70. / Gärtner, Jutta; Brosius, Ute; Obie, Cassandra; Watkins, Paul A; Valle, David.

In: European Journal of Cell Biology, Vol. 76, No. 4, 1998, p. 237-245.

Research output: Contribution to journalArticle

Gärtner, Jutta ; Brosius, Ute ; Obie, Cassandra ; Watkins, Paul A ; Valle, David. / Restoration of PEX2 peroxisome assembly defects by overexpression of PMP70. In: European Journal of Cell Biology. 1998 ; Vol. 76, No. 4. pp. 237-245.
@article{6de9aeae367044e2bda2a374ababc20e,
title = "Restoration of PEX2 peroxisome assembly defects by overexpression of PMP70",
abstract = "The mutant Chinese hamster ovary (CHO) cell line Z78/C has defective peroxisome assembly due to a missense mutation in PEX2, the gene which encodes the 35 kDa peroxisomal integral membrane protein. In humans, PEX2 mutations are responsible for complementation group 10 of the human peroxisome biogenesis disorders (PBD), a genetically heterogeneous group of lethal, autosomal recessive diseases including the Zellweger syndrome and related phenotypes. To develop additional cellular models for Zellweger syndrome, we produced a series of new mutant CHO cell clones in the same complementation group as Z78/C (Z2, Z7, Z22, and Z105). As expected, expression of human PEX2 restores peroxisomal biogenesis in all of these clones. Surprisingly expression of the human 70 kDa peroxisomal membrane protein (PMP70) also restores peroxisome biogenesis in these same CHO cell clones. We confirmed this effect of PMP70 expression on peroxisome biogenesis by determining the subcellular latency of catalase, the immunohistochemical localization of catalase and the β-oxidation of very long chain fatty acids (VLCFA). By contrast, expression of a mutant allele of PMP70 identified in a patient with Zellweger syndrome did not restore peroxisome biogenesis in the PEX2-deficient CHO cell clones. Our results indicate that overexpression of PMP70 suppresses the phenotype of PEX2 gene mutations. These observations suggest a functional interaction between PEX2 and PMP70 in the peroxisome membrane.",
keywords = "Gene expression, Human peroxisomal membrane proteins, Peroxisome, Peroxisome assembly mutants, Peroxisome biogenesis disorders",
author = "Jutta G{\"a}rtner and Ute Brosius and Cassandra Obie and Watkins, {Paul A} and David Valle",
year = "1998",
language = "English (US)",
volume = "76",
pages = "237--245",
journal = "European Journal of Cell Biology",
issn = "0171-9335",
publisher = "Urban und Fischer Verlag GmbH und Co. KG",
number = "4",

}

TY - JOUR

T1 - Restoration of PEX2 peroxisome assembly defects by overexpression of PMP70

AU - Gärtner, Jutta

AU - Brosius, Ute

AU - Obie, Cassandra

AU - Watkins, Paul A

AU - Valle, David

PY - 1998

Y1 - 1998

N2 - The mutant Chinese hamster ovary (CHO) cell line Z78/C has defective peroxisome assembly due to a missense mutation in PEX2, the gene which encodes the 35 kDa peroxisomal integral membrane protein. In humans, PEX2 mutations are responsible for complementation group 10 of the human peroxisome biogenesis disorders (PBD), a genetically heterogeneous group of lethal, autosomal recessive diseases including the Zellweger syndrome and related phenotypes. To develop additional cellular models for Zellweger syndrome, we produced a series of new mutant CHO cell clones in the same complementation group as Z78/C (Z2, Z7, Z22, and Z105). As expected, expression of human PEX2 restores peroxisomal biogenesis in all of these clones. Surprisingly expression of the human 70 kDa peroxisomal membrane protein (PMP70) also restores peroxisome biogenesis in these same CHO cell clones. We confirmed this effect of PMP70 expression on peroxisome biogenesis by determining the subcellular latency of catalase, the immunohistochemical localization of catalase and the β-oxidation of very long chain fatty acids (VLCFA). By contrast, expression of a mutant allele of PMP70 identified in a patient with Zellweger syndrome did not restore peroxisome biogenesis in the PEX2-deficient CHO cell clones. Our results indicate that overexpression of PMP70 suppresses the phenotype of PEX2 gene mutations. These observations suggest a functional interaction between PEX2 and PMP70 in the peroxisome membrane.

AB - The mutant Chinese hamster ovary (CHO) cell line Z78/C has defective peroxisome assembly due to a missense mutation in PEX2, the gene which encodes the 35 kDa peroxisomal integral membrane protein. In humans, PEX2 mutations are responsible for complementation group 10 of the human peroxisome biogenesis disorders (PBD), a genetically heterogeneous group of lethal, autosomal recessive diseases including the Zellweger syndrome and related phenotypes. To develop additional cellular models for Zellweger syndrome, we produced a series of new mutant CHO cell clones in the same complementation group as Z78/C (Z2, Z7, Z22, and Z105). As expected, expression of human PEX2 restores peroxisomal biogenesis in all of these clones. Surprisingly expression of the human 70 kDa peroxisomal membrane protein (PMP70) also restores peroxisome biogenesis in these same CHO cell clones. We confirmed this effect of PMP70 expression on peroxisome biogenesis by determining the subcellular latency of catalase, the immunohistochemical localization of catalase and the β-oxidation of very long chain fatty acids (VLCFA). By contrast, expression of a mutant allele of PMP70 identified in a patient with Zellweger syndrome did not restore peroxisome biogenesis in the PEX2-deficient CHO cell clones. Our results indicate that overexpression of PMP70 suppresses the phenotype of PEX2 gene mutations. These observations suggest a functional interaction between PEX2 and PMP70 in the peroxisome membrane.

KW - Gene expression

KW - Human peroxisomal membrane proteins

KW - Peroxisome

KW - Peroxisome assembly mutants

KW - Peroxisome biogenesis disorders

UR - http://www.scopus.com/inward/record.url?scp=0031663426&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031663426&partnerID=8YFLogxK

M3 - Article

VL - 76

SP - 237

EP - 245

JO - European Journal of Cell Biology

JF - European Journal of Cell Biology

SN - 0171-9335

IS - 4

ER -