Identification and characterization of human PMP34, a protein closely related to the peroxisomal integral membrane protein PMP47 of Candida boidinii

Abstract

The cDNA of a human protein displaying 33% identity to the peroxisomal integral membrane protein PMP47 of Candida boidinii (CbPMP47) was cloned. It encodes a protein of 307 amino acids, with a calculated molecular mass of 34566 Da. The protein, which we name HsPMP34, contains six membrane spans and belongs, like PMP47, to the family of mitochondrial solute carriers. Based on overlapping available expressed sequence tags (ESTs) combined with the sequencing of one EST, the amino acid sequence of the mouse counterpart (molecular mass of 34 422 Da) could also be deduced. By means of reverse-transcription PCR, the presence of PMP34 mRNA was revealed in liver of man and in liver and other tissues of mouse and rat. The human gene is localized to chromosome 22q13. Given the similarity of HsPMP34 not only to CbPMP47 but also to known or putative mitochondrial transporters, its subcellular localization was investigated. Fluorescence microscopy of HepG2 cells or mouse fibroblasts transfected with a plasmid encoding a HsPMP34/green fluorescent fusion protein revealed a punctate pattern, reminiscent of a peroxisomal distribution. By indirect immunofluorescence, the HsPMP34/green fluorescent fusion protein clearly colocalized with the dimeric peroxisomal thiolase. Upon transfection of mouse fibroblasts lacking functional peroxisomes due the knock-out of PEX5 [Baes, M., Gressens, P., Baumgart, E., Carmeliet, P., Casteels, M., Fransen, M., Evrard, P., Fahimi, D., Declercq, P. E., Collen, D., Van Veldhoven, P. P. & Mannaerts, G. P. (1997) Nat. Genet. 17, 49Ϫ53], fluorescence was associated with larger and less-abundant structures. Taken together, the data indicate that HsPMP34 is a peroxisomal membrane protein and is either the human counterpart of CbPMP47 or closely related to it. According to its structure, the protein is most probably involved in transport.

The Human PICD Gene Encodes a Cytoplasmic and Peroxisomal NADP+-dependent Isocitrate Dehydrogenase

“…This hypothesis predicts the existence of multiple transporters to mediate the exchange of metabolites between the peroxisome and cytoplasm. Consistent with this idea, mammalian peroxisomes have been shown to contain at least four members of the ATP-binding cassette family of transmembrane transporters (46 -49) and two members of the solute carrier family of antiporters (50).…”

Identification of a Peroxisomal ATP Carrier Required for Medium-Chain Fatty Acid β-Oxidation and Normal Peroxisome Proliferation in Saccharomyces cerevisiae

“…In this paper we report on the S. cerevisiae orthologue of human PMP34 (53) and Candida boidinii PMP47 (23), YPR128cp, which is a member of the mitochondrial carrier family (MCF) of solute transporters, which includes carriers like the ADP/ATP carrier, the dicarboxylate carrier a.o (25). We show that YPR128cp is functionally involved in MCFA ␤-oxidation and peroxisome proliferation and we conclude that YPR128cp mediates the transport of ATP across the peroxisomal membrane.…”

Biochemistry and genetics of inherited disorders of peroxisomal fatty acid metabolism

“…CoA, although being present in peroxisomes ( 72 ), is not available for this reaction, and a transporter is not known. SLC25A17, a member of the mitochondrial solute transporters (better known as PMP34) is described as a peroxisomal ATP transporter ( 73,74 ). The phytol-induced pathology seen in Slc25a17 Ϫ / Ϫ mice, with accumulation of phytanic and pristanic acid (E. Van Ael, M. Baes, and P.P.…”