PEX11alpha is required for peroxisome proliferation in response to 4-phenylbutyrate but is dispensable for peroxisome proliferator-activated receptor alpha-mediated peroxisome proliferation.
The PEX11 peroxisomal membrane proteins promote peroxisome division in multiple eukaryotes. As part of our effort to understand the molecular and physiological functions of PEX11 proteins, we disrupted the mouse PEX11alpha gene. Overexpression of PEX11alpha is sufficient to promote peroxisome division, and a class of chemicals known as peroxisome proliferating agents (PPAs) induce the expression of PEX11alpha and promote peroxisome division. These observations led to the hypothesis that PPAs induce peroxisome abundance by enhancing PEX11alpha expression. The phenotypes of PEX11alpha(-/-) mice indicate that this hypothesis remains valid for a novel class of PPAs that act independently of peroxisome proliferator-activated receptor alpha (PPARalpha) but is not valid for the classical PPAs that act as activators of PPARalpha. Furthermore, we find that PEX11alpha(-/-) mice have normal peroxisome abundance and that cells lacking both PEX11alpha and PEX11beta, a second mammalian PEX11 gene, have no greater defect in peroxisome abundance than do cells lacking only PEX11beta. Finally, we report the identification of a third mammalian PEX11 gene, PEX11gamma, and show that it too encodes a peroxisomal protein.
Li
Xiaoling
X
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Baumgart
Eveline
E
Dong
Gao-Xiang
GX
Morrell
James C
JC
Jimenez-Sanchez
Gerardo
G
Valle
David
D
Smith
Kirby D
KD
Gould
Stephen J
SJ
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D004032:Diet; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D018390:Gene Targeting; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008928:Mitochondria / Q000648:ultrastructure; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D020025:Peroxisome Proliferators / Q000008:administration & dosage / Q000494:pharmacology*; D020675:Peroxisomes / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D010641:Phenotype; D010654:Phenylbutyrates / Q000494:pharmacology*; D010802:Phylogeny; D010955:Plasmalogens / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D016415:Sequence Alignment; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism*
D000970:Antineoplastic Agents; D005227:Fatty Acids; D008565:Membrane Proteins; C486770:PEX11G protein, human; D020025:Peroxisome Proliferators; C469727:Pex11alpha protein, mouse; C490452:Pex11b protein, mouse; C469728:Pex11c protein, mouse; D010654:Phenylbutyrates; D010955:Plasmalogens; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C075773:4-phenylbutyric acid