Transmembrane protein 135 regulates lipid homeostasis through its role in peroxisomal DHA metabolism

• DOI: 10.1038/s42003-022-04404-7
• Publication Date: 2023-01-04T09:03:04Z
• Authors: Michael Landowski; Vijesh J. Bhute; Samuel Grindel; Zachary Haugstad; Yeboah K. Gyening; Madison Tytanic; Richard S. Brush; Lucas J. Moyer; David W. Nelson; Christopher R. Davis; Chi-Liang Eric Yen; Sakae Ikeda; Martin-Paul Agbaga; Akihiro Ikeda
• Keywords: 0303 health sciences; Docosahexaenoic Acids; QH301-705.5; Peroxisome Proliferator-Activated Receptors; Membrane Proteins; Lipid Metabolism; Article; Mitochondrial Proteins; Mice; 03 medical and health sciences; Peroxisomes; Animals; Homeostasis; Biology (General); Oxidation-Reduction

Abstract Transmembrane protein 135 (TMEM135) is thought to participate in the cellular response increased intracellular lipids yet no defined molecular function for TMEM135 lipid metabolism has been identified. In this study, we performed a analysis of tissues from Tmem135 mutant mice and found striking reductions docosahexaenoic acid (DHA) across all tissues, indicating role production DHA. Since enzymes required DHA synthesis remain intact mice, hypothesized that involved export peroxisomes. The mutation likely leads retention peroxisomes, causing be degraded within peroxisomes by their beta-oxidation machinery. This may lead generation or alteration ligands activation peroxisome proliferator-activated receptor (PPARa) signaling, which turn could result peroxisomal number observed mice. We confirmed effect PPARa signaling detecting decreased proteins upon genetic ablation Ppara Using also validated protective on metabolic disease phenotypes leptin previous studies. Thus, conclude homeostasis through its