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-Structure paper
タイトル | METTL17 is an Fe-S cluster checkpoint for mitochondrial translation. |
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ジャーナル・号・ページ | Mol Cell, Vol. 84, Issue 2, Page 359-374.e8, Year 2024 |
掲載日 | 2024年1月18日 |
著者 | Tslil Ast / Yuzuru Itoh / Shayan Sadre / Jason G McCoy / Gil Namkoong / Jordan C Wengrod / Ivan Chicherin / Pallavi R Joshi / Piotr Kamenski / Daniel L M Suess / Alexey Amunts / Vamsi K Mootha / |
PubMed 要旨 | Friedreich's ataxia (FA) is a debilitating, multisystemic disease caused by the depletion of frataxin (FXN), a mitochondrial iron-sulfur (Fe-S) cluster biogenesis factor. To understand the cellular ...Friedreich's ataxia (FA) is a debilitating, multisystemic disease caused by the depletion of frataxin (FXN), a mitochondrial iron-sulfur (Fe-S) cluster biogenesis factor. To understand the cellular pathogenesis of FA, we performed quantitative proteomics in FXN-deficient human cells. Nearly every annotated Fe-S cluster-containing protein was depleted, indicating that as a rule, cluster binding confers stability to Fe-S proteins. We also observed depletion of a small mitoribosomal assembly factor METTL17 and evidence of impaired mitochondrial translation. Using comparative sequence analysis, mutagenesis, biochemistry, and cryoelectron microscopy, we show that METTL17 binds to the mitoribosomal small subunit during late assembly and harbors a previously unrecognized [FeS] cluster required for its stability. METTL17 overexpression rescued the mitochondrial translation and bioenergetic defects, but not the cellular growth, of FXN-depleted cells. These findings suggest that METTL17 acts as an Fe-S cluster checkpoint, promoting translation of Fe-S cluster-rich oxidative phosphorylation (OXPHOS) proteins only when Fe-S cofactors are replete. |
リンク | Mol Cell / PubMed:38199006 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.25 - 2.87 Å |
構造データ | EMDB-16966, PDB-8om2: EMDB-16967, PDB-8om3: EMDB-16968, PDB-8om4: EMDB-17089: Small subunit of yeast mitochondrial ribosome in complex with METTL17/Rsm22 (overall refinement) EMDB-17090: Small subunit of yeast mitochondrial ribosome in complex with METTL17/Rsm22 (local-masked refined on the body) EMDB-17091: Small subunit of yeast mitochondrial ribosome in complex with METTL17/Rsm22 (local-masked refined on the head) EMDB-17092: Small subunit of yeast mitochondrial ribosome in complex with METTL17/Rsm22 (local-masked refined on the tail) EMDB-17093: Small subunit of yeast mitochondrial ribosome in complex with METTL17/Rsm22 (local-masked refined on METTL17/Rsm22) EMDB-17094: Small subunit of yeast mitochondrial ribosome in complex with IF3/Aim23 (overall refinement) EMDB-17095: Small subunit of yeast mitochondrial ribosome in complex with IF3/Aim23 (local-masked refined on the body) EMDB-17096: Small subunit of yeast mitochondrial ribosome in complex with IF3/Aim23 (local-masked refined on the head) EMDB-17097: Small subunit of yeast mitochondrial ribosome in complex with IF3/Aim23 (local-masked refined on the tail) EMDB-17098: Small subunit of yeast mitochondrial ribosome (overall refinement) EMDB-17099: Small subunit of yeast mitochondrial ribosome (local-masked refined on the body) EMDB-17100: Small subunit of yeast mitochondrial ribosome(local-masked refined on the head) EMDB-17101: Small subunit of yeast mitochondrial ribosome(local-masked refined on the tail) EMDB-17102: Small subunit of yeast mitochondrial ribosome(local-masked refined on the helix bundle) |
化合物 | ChemComp-MG: ChemComp-K: ChemComp-LMT: ChemComp-ATP: ChemComp-SF4: ChemComp-HOH: |
由来 |
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キーワード | RIBOSOME / mitochondria / assembly / biogenesis / iron-sulfur cluster / 4Fe-4S / initiation factor 3 / pre-initiation complex |