論文 - 詳細
| RRC ID | 59511 |
|---|---|
| 著者 | Hsiung KC, Liu KY, Tsai TF, Yoshina S, Mitani S, Chin-Ming Tan B, Lo SJ. |
| タイトル | Defects in CISD-1, a mitochondrial iron-sulfur protein, lower glucose level and ATP production in Caenorhabditis elegans. |
| ジャーナル | Biomed J |
| Abstract |
BACKGROUND:CDGSH iron sulfur domain-containing protein 1 (CISD-1) belongs to the CISD protein family that is evolutionary conserved across different species. In mammals, CISD-1 protein has been implicated in diseases such as cancers and diabetes. As a tractable model organism to study disease-associated proteins, we employed Caenorhabditis elegans in this study with an aim to establish a model for interrogating the functional relevance of CISD-1 in human metabolic conditions. METHODS:We first bioinformatically identified the human Cisd-1 homologue in worms. We then employed N2 wild-type and cisd-1(tm4993) mutant to investigate the consequences of CISD-1 loss-of-function on: 1) the expression pattern of CISD-1, 2) mitochondrial morphology pattern, 3) mitochondrial function and bioenergetics, and 4) the effects of anti-diabetes drugs. RESULTS:We first identified C. elegans W02B12.15 gene as the human Cisd-1 homologous gene, and pinpointed the localization of CISD-1 to the outer membrane of mitochondria. As compared with the N2 wild-type worm, cisd-1(tm4993) mutant exhibited a higher proportion of hyperfused form of mitochondria. This structural abnormality was associated with the generation of higher levels of ROS and mitochondrial superoxide but lower ATP. These physiological changes in mutants did not result in discernable effects on animal motility and lifespan. Moreover, the amount of glucose in N2 wild-type worms treated with troglitazone and pioglitazone, derivatives of TZD, was reduced to a comparable level as in the mutant animals. CONCLUSIONS:By focusing on the Cisd-1 gene, our study established a C. elegans genetic system suitable for modeling human diabetes-related diseases. |
| 巻・号 | 43(1) |
| ページ | 32-43 |
| 公開日 | 2020-2-1 |
| DOI | 10.1016/j.bj.2019.07.009 |
| PII | S2319-4170(19)30480-9 |
| PMID | 32200954 |
| PMC | PMC7090286 |
| MeSH | Adenosine Triphosphate / metabolism* Animals Caenorhabditis elegans Caenorhabditis elegans Proteins / metabolism Energy Metabolism / genetics Glucose / metabolism* Iron-Sulfur Proteins / genetics Iron-Sulfur Proteins / metabolism Longevity / genetics Mitochondria / metabolism* Mitochondrial Proteins / deficiency Mitochondrial Proteins / genetics* |
| IF | 3.697 |
| 引用数 | 1 |
| リソース情報 | |
| 線虫 | tm4993 |