Overexpression of human acyl-CoA thioesterase upregulates peroxisome biogenesis.
The biological functions of human acyl-CoA thioesterase III (ACTEIII/PTE-1), initially identified as an HIV-1 Nef binding protein, have remained unclear. We report herein that the stable overexpression of ACTEIII/PTE-1 in human and murine T-cell lines resulted in an increase in both peroxisome number and lipid droplet formation in a manner dependent on the amount of the protein. Peroxisome proliferation was evidenced by immunofluorescence staining for catalase, a peroxisome marker protein, as well as by direct peroxisome enumeration on electron micrographs. Consistently, the amount of catalase was elevated as the amount of ACTEIII/PTE-1 was increased. ACTEIII/PTE-1 mutants with reduced enzymatic activity or with the defect in peroxisome localization did not induce peroxisome proliferation, indicating that peroxisome proliferation was mediated by metabolites generated by ACTEIII/PTE-1 within peroxisomes. Finally, thymocytes isolated from a T-cell-specific ACTEIII/PTE-1 transgenic mouse as well as human and murine cell lines of lymphoid and non-lymphoid origins exhibited a similar proliferation of peroxisomes. Thus, ACTEIII/PTE-1 may be involved in the metabolic regulation of peroxisome proliferation.
Ishizuka
Mitsuru
M
Department of Anatomy and Developmental Biology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Toyama
Yoshiro
Y
Watanabe
Hiroyuki
H
Fujiki
Yukio
Y
Takeuchi
Arata
A
Yamasaki
Sho
S
Yuasa
Shigeki
S
Miyazaki
Masaru
M
Nakajima
Nobuyuki
N
Taki
Shinsuke
S
Saito
Takashi
T
D000818:Animals; D015415:Biomarkers; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D004734:Energy Metabolism / Q000235:genetics; D005455:Fluorescent Antibody Technique; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D050356:Lipid Metabolism; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D015388:Organelles / Q000201:enzymology* / Q000648:ultrastructure; D010170:Palmitoyl-CoA Hydrolase / Q000235:genetics / Q000378:metabolism*; D020675:Peroxisomes / Q000201:enzymology* / Q000648:ultrastructure; D013601:T-Lymphocytes / Q000201:enzymology* / Q000648:ultrastructure; D013869:Thiolester Hydrolases / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
D015415:Biomarkers; D002374:Catalase; D013869:Thiolester Hydrolases; C413373:ACOT2 protein, human; C106353:ACOT8 protein, human; D010170:Palmitoyl-CoA Hydrolase