論文 - 詳細
| RRC ID | 32240 |
|---|---|
| 著者 | Walter KM, Schönenberger MJ, Trötzmüller M, Horn M, Elsässer HP, Moser AB, Lucas MS, Schwarz T, Gerber PA, Faust PL, Moch H, Köfeler HC, Krek W, Kovacs WJ. |
| タイトル | Hif-2α promotes degradation of mammalian peroxisomes by selective autophagy. |
| ジャーナル | Cell Metab |
| Abstract |
Peroxisomes play a central role in lipid metabolism, and their function depends on molecular oxygen. Low oxygen tension or von Hippel-Lindau (Vhl) tumor suppressor loss is known to stabilize hypoxia-inducible factors alpha (Hif-1α and Hif-2α) to mediate adaptive responses, but it remains unknown if peroxisome homeostasis and metabolism are interconnected with Hif-α signaling. By studying liver-specific Vhl, Vhl/Hif1α, and Vhl/Hif2α knockout mice, we demonstrate a regulatory function of Hif-2α signaling on peroxisomes. Hif-2α activation augments peroxisome turnover by selective autophagy (pexophagy) and thereby changes lipid composition reminiscent of peroxisomal disorders. The autophagy receptor Nbr1 localizes to peroxisomes and is likewise degraded by Hif-2α-mediated pexophagy. Furthermore, we demonstrate that peroxisome abundance is reduced in VHL-deficient human clear cell renal cell carcinomas with high HIF-2α levels. These results establish Hif-2α as a negative regulator of peroxisome abundance and metabolism and suggest a mechanism by which cells attune peroxisomal function with oxygen availability. |
| 巻・号 | 20(5) |
| ページ | 882-897 |
| 公開日 | 2014-11-4 |
| DOI | 10.1016/j.cmet.2014.09.017 |
| PII | S1550-4131(14)00440-9 |
| PMID | 25440060 |
| MeSH | Animals Autophagy* Basic Helix-Loop-Helix Transcription Factors / genetics Basic Helix-Loop-Helix Transcription Factors / metabolism* Carcinoma, Renal Cell / genetics Carcinoma, Renal Cell / metabolism Cell Line, Tumor Gene Deletion Gene Expression Regulation, Neoplastic Humans Kidney / metabolism Kidney Neoplasms / genetics Kidney Neoplasms / metabolism Mice Mice, Knockout Peroxisomes / genetics Peroxisomes / metabolism* Von Hippel-Lindau Tumor Suppressor Protein / genetics Von Hippel-Lindau Tumor Suppressor Protein / metabolism |
| IF | 21.567 |
| 引用数 | 65 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC02759 |