Interplay between hepatic mitochondria-associated membranes, lipid metabolism and caveolin-1 in mice.
Interplay between hepatic mitochondria-associated membranes, lipid metabolism and caveolin-1 in mice.
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DOI：
10.1038/srep27351
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发表时间：
2016-06-06
影响因子：
4.6
通讯作者：
Del Pozo MA
中科院分区：
文献类型：
--
作者：
Sala-Vila A;Navarro-Lérida I;Sánchez-Alvarez M;Bosch M;Calvo C;López JA;Calvo E;Ferguson C;Giacomello M;Serafini A;Scorrano L;Enriquez JA;Balsinde J;Parton RG;Vázquez J;Pol A;Del Pozo MA
线粒体相关膜（MAM）是内质网（ER）的一个特殊亚域，作为细胞内信号中枢。MAM功能障碍与肝脏疾病有关。我们报告了一项基于高通量质谱的小鼠肝脏MAMs蛋白质组学表征，该表征将其描述为参与不同代谢过程（包括类固醇代谢）的极其复杂的隔室。有趣的是，我们发现CAV1是肝脏MAMs的一个组成部分，它决定了这些内质网亚域的相对胆固醇含量。最后，对野生型和CAV1缺陷小鼠的MAMs进行了详细的蛋白质组学比较分析，结果表明，功能性CAV1有助于MAMs积累的细胞内类固醇和脂蛋白代谢相关过程的募集和调节。讨论了CAV1生物学的这些新方面对全球细胞稳态和疾病的潜在影响。
The mitochondria-associated membrane (MAM) is a specialized subdomain of the endoplasmic reticulum (ER) which acts as an intracellular signaling hub. MAM dysfunction has been related to liver disease. We report a high-throughput mass spectrometry-based proteomics characterization of MAMs from mouse liver, which portrays them as an extremely complex compartment involved in different metabolic processes, including steroid metabolism. Interestingly, we identified caveolin-1 (CAV1) as an integral component of hepatic MAMs, which determine the relative cholesterol content of these ER subdomains. Finally, a detailed comparative proteomics analysis between MAMs from wild type and CAV1-deficient mice suggests that functional CAV1 contributes to the recruitment and regulation of intracellular steroid and lipoprotein metabolism-related processes accrued at MAMs. The potential impact of these novel aspects of CAV1 biology on global cell homeostasis and disease is discussed.