論文 - 詳細
| RRC ID | 88136 |
|---|---|
| 著者 | Li Q, Weiss K, Niwa F, Riemer J, Hoppe T. |
| タイトル | Leucine inhibits degradation of outer mitochondrial membrane proteins to adapt mitochondrial respiration. |
| ジャーナル | Nat Cell Biol |
| Abstract |
The mitochondrial proteome is remodelled to meet metabolic demands, but how metabolic cues regulate mitochondrial protein turnover remains unclear. Here we identify a conserved, nutrient-responsive mechanism in which the amino acid leucine suppresses ubiquitin-dependent degradation of outer mitochondrial membrane (OMM) proteins, stabilizing key components of the protein import machinery and expanding the mitochondrial proteome to enhance metabolic respiration. Leucine inhibits the amino acid sensor GCN2, which selectively reduces the E3 ubiquitin ligase cofactor SEL1L at mitochondria. Depletion of SEL1L phenocopies the effect of leucine, elevating OMM protein abundance and mitochondrial respiration. Disease-associated defects in leucine catabolism and OMM protein turnover impair fertility in Caenorhabditis elegans and render human lung cancer cells resistant to inhibition of mitochondrial protein import. These findings define a leucine-GCN2-SEL1L axis that links nutrient sensing to mitochondrial proteostasis, with implications for metabolic disorders and cancer. |
| 巻・号 | 27(11) |
| ページ | 1889-1901 |
| 公開日 | 2025-11-1 |
| DOI | 10.1038/s41556-025-01799-3 |
| PII | 10.1038/s41556-025-01799-3 |
| PMID | 41174002 |
| PMC | PMC12611767 |
| MeSH | Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Cell Respiration Humans Leucine* / metabolism Leucine* / pharmacology Mitochondria* / drug effects Mitochondria* / metabolism Mitochondrial Membranes* / drug effects Mitochondrial Membranes* / metabolism Mitochondrial Proteins* / genetics Mitochondrial Proteins* / metabolism Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism Proteolysis / drug effects Ubiquitin-Protein Ligases / genetics Ubiquitin-Protein Ligases / metabolism |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 106 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 98.5 |
| リソース情報 | |
| 線虫 | tm544 |