School of Public Health and Management, Wenzhou Medical University, Wenzhou, 325035, China.
Department of Food Science and Engineering, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, China.
Mol Nutr Food Res. 2021 Jul;65(14):e2001076. doi: 10.1002/mnfr.202001076. Epub 2021 Jun 14.
Mitochondria-associated membrane (MAM) connects endoplasmic reticulum (ER) and mitochondria plays a significant role in lipid metabolism and Ca homeostasis. Albeit sulforaphane (SFN) shows potential in ameliorating excessive fat accumulation and mitochondrial function; whether MAM is a target of SFN and its underlying mechanisms are still unclear.
High-fat-intake models are established both in vivo and in vitro. SFN widens the distance between ER and mitochondria and down-regulates MAM tether protein mitofusin-2. SFN reverses the increase of Ca induced by fatty acid and inhibits the Ca channel inositol-1,4,5-trisphosphate receptor (IP3R). Compared with high fat group, SFN alleviates Ca overload in the mitochondria and suppresses mitochondrial calcium uniporter (MCU). Furthermore, SFN increases mitochondrial DNA quantities and mitochondria membrane potential, while decreasing reactive oxygen species (ROS) production. Finally, SFN increases mitochondria complexes IV content and ATP synthesis.
These results suggest that SFN balances the Ca homeostasis in the MAM through regulating Ca flux by Ca channel IP3R and MCU.
线粒体相关膜（MAM）连接内质网（ER）和线粒体，在脂质代谢和 Ca 稳态中发挥重要作用。尽管萝卜硫素（SFN）在改善脂肪积累过多和线粒体功能方面显示出潜力；但 MAM 是否是 SFN 的靶点及其潜在机制尚不清楚。
在体内和体外均建立高脂肪摄入模型。SFN 扩大 ER 和线粒体之间的距离，并下调 MAM 连接蛋白线粒体融合蛋白-2。SFN 逆转脂肪酸引起的 Ca 增加，并抑制 Ca 通道三磷酸肌醇受体（IP3R）。与高脂肪组相比，SFN 减轻线粒体中的 Ca 过载并抑制线粒体钙单向转运蛋白（MCU）。此外，SFN 增加线粒体 DNA 数量和线粒体膜电位，同时减少活性氧（ROS）的产生。最后，SFN 增加线粒体复合物 IV 的含量和 ATP 的合成。
这些结果表明，SFN 通过调节 Ca 通道 IP3R 和 MCU 来调节 Ca 流，从而在 MAM 中平衡 Ca 稳态。
