Sulforaphane Balances Ca 2+ Homeostasis Injured by Excessive Fat via Mitochondria-Associated Membrane (MAM).

Scope Mitochondria-associated membrane (MAM) connecting endoplasmic reticulum (ER) and mitochondria plays a significant role in lipid metabolism and Ca2+ homeostasis. Albeit sulforaphane (SFN) shows potential in ameliorating excessive fat accumulation and mitochondrial function, whether MAM is a target of SFN and its underling mechanisms are still unclear. Methods and results High-fat-intake models are established both in vivo and in vitro. SFN widened the distance between ER and mitochondria and down-regulated MAM tether protein mitofusin-2. SFN reversed the increase of Ca2+ induced by fatty acid and inhibited the Ca2+ channel IP3R. Compared with high fat group, SFN alleviate Ca2+ overload in the mitochondria and suppressing mitochondrial calcium uniporter (MCU). Furthermore, SFN increased mitochondrial DNA quantities and mitochondria membrane potential, while decreased ROS production. Finally, SFN increased mitochondria complexes IV content and ATP synthesis. Conclusion These results suggested that SFN balanced the Ca2+ homeostasis in the MAM through regulating Ca2+ flux by Ca2+ channel IP3R and MCU. This article is protected by copyright. All rights reserved.