PPARα regulates acyl-CoA oxidase 1 (ACOX1) but not catalase

Xue Chen; Anna Mazur; Wei Xu; W Christopher Risher; Krista L Denning; Yongke Lu

doi:10.1016/j.bbrc.2025.152247

PPARα regulates acyl-CoA oxidase 1 (ACOX1) but not catalase

Biochem Biophys Res Commun. 2025 Jun 25:777:152247. doi: 10.1016/j.bbrc.2025.152247. Online ahead of print.

Authors

Xue Chen¹, Anna Mazur¹, Wei Xu¹, W Christopher Risher¹, Krista L Denning², Yongke Lu³

Affiliations

¹ Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1700 3rd Avenue, Huntington, WV, 25755, USA.
² Department of Pathology, Joan C. Edwards School of Medicine, Marshall University, 1700 3rd Avenue, Huntington, WV, 25755, USA.
³ Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1700 3rd Avenue, Huntington, WV, 25755, USA. Electronic address: luy@marshall.edu.

PMID: 40580723
DOI: 10.1016/j.bbrc.2025.152247

Abstract

Peroxisomes are membranous organelles, and peroxisomal membrane protein 70 (PMP70), a peroxisome transporter, is used as a marker of peroxisomes. Like mitochondria, peroxisomes can also oxidize fatty acids and its rate limiting enzyme is acyl-CoA oxidase 1 (ACOX1). But unlike mitochondria, peroxisomes generate hydrogen peroxide (H₂O₂) by ACOX1, and the generated H₂O₂ is locally detoxified by catalase. PPARα agonist WY-14,643 induces peroxisome proliferation as indicated by the induction of PMP70, ACOX1 and catalase were also induced. However, ACOX1 was induced to a greater extent than catalase. After WY-14,643 withdrawal, the induced ACOX1 started to decrease after 2 days; but catalase remained at higher levels up to10 days. While mRNA levels of ACOX1 were also induced by WY-14,643, mRNA levels of catalase were not induced by WY-14,643. In the livers collected from liver-specific PEX16 knockout (Pex16^Alb-Cre) mice, peroxisomes are absent but catalase and ACOX1 were somehow upregulated. The mRNA of ACOX1 was also spontaneously elevated, but the catalase mRNA was not changed. When PPARα was abrogated through crossing the Pex16^Alb-Cre mice with Pparα^-/- mice to create the Pparα^-/-/Pex16^Alb-Cre mice, the upregulated ACOX1 protein was suppressed in the Pparα^-/-/Pex16^Alb-Cre mice, but catalase protein remained elevated. These results suggest that ACOX1 but not catalase is regulated by PPARα.

Keywords: CYP4A; PEX16; PMP70; Peroxisome proliferation; WY-14,643.