論文 - 詳細
| RRC ID | 59350 |
|---|---|
| 著者 | Hada K, Hirota K, Inanobe A, Kako K, Miyata M, Araoi S, Matsumoto M, Ohta R, Arisawa M, Daitoku H, Hanada T, Fukamizu A. |
| タイトル | Tricarboxylic acid cycle activity suppresses acetylation of mitochondrial proteins during early embryonic development in Caenorhabditis elegans. |
| ジャーナル | J Biol Chem |
| Abstract |
The tricarboxylic acid (TCA) cycle (or citric acid cycle) is responsible for the complete oxidation of acetyl-CoA and formation of intermediates required for ATP production and other anabolic pathways, such as amino acid synthesis. Here, we uncovered an additional mechanism that may help explain the essential role of the TCA cycle in the early embryogenesis of Caenorhabditis elegans. We found that knockdown of citrate synthase (cts-1), the initial and rate-limiting enzyme of the TCA cycle, results in early embryonic arrest, but that this phenotype is not because of ATP and amino acid depletions. As a possible alternative mechanism explaining this developmental deficiency, we observed that cts-1 RNAi embryos had elevated levels of intracellular acetyl-CoA, the starting metabolite of the TCA cycle. Of note, we further discovered that these embryos exhibit hyperacetylation of mitochondrial proteins. We found that supplementation with acetylase-inhibiting polyamines, including spermidine and putrescine, counteracted the protein hyperacetylation and developmental arrest in the cts-1 RNAi embryos. Contrary to the hypothesis that spermidine acts as an acetyl sink for elevated acetyl-CoA, the levels of three forms of acetylspermidine, N1-acetylspermidine, N8-acetylspermidine, and N1,N8-diacetylspermidine, were not significantly increased in embryos treated with exogenous spermidine. Instead, we demonstrated that the mitochondrial deacetylase sirtuin 4 (encoded by the sir-2.2 gene) is required for spermidine's suppression of protein hyperacetylation and developmental arrest in the cts-1 RNAi embryos. Taken together, these results suggest the possibility that during early embryogenesis, acetyl-CoA consumption by the TCA cycle in C. elegans prevents protein hyperacetylation and thereby protects mitochondrial function. |
| 巻・号 | 294(9) |
| ページ | 3091-3099 |
| 公開日 | 2019-3-1 |
| DOI | 10.1074/jbc.RA118.004726 |
| PII | S0021-9258(20)39244-9 |
| PMID | 30606736 |
| PMC | PMC6398127 |
| MeSH | Acetylation Adenosine Triphosphate / metabolism Animals Aspartic Acid / metabolism Caenorhabditis elegans / cytology Caenorhabditis elegans / embryology* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Citrate (si)-Synthase / deficiency Citrate (si)-Synthase / genetics Citric Acid / metabolism Citric Acid Cycle* Embryonic Development* Glutamic Acid / metabolism Intracellular Space / metabolism Mitochondrial Proteins / metabolism* Time Factors |
| IF | 4.106 |
| 引用数 | 3 |
| 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 | 9 |
| 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 | |
| 線虫 | tm2468 |