Sulforaphane Balances Ca2+ Homeostasis Injured by Excessive Fat via Mitochondria-Associated Membrane (MAM)

Scope Mitochondria-associated membrane (MAM) connects 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 underlying mechanisms are still unclear. Methods and Results 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 Ca2+ induced by fatty acid and inhibits the Ca2+ channel inositol-1,4,5-trisphosphate receptor (IP3R). Compared with high fat group, SFN alleviates Ca2+ 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. Conclusion These results suggest that SFN balances the Ca2+ homeostasis in the MAM through regulating Ca2+ flux by Ca2+ channel IP3R and MCU.

Automated summary

The study revealed that SFN balances Ca2+ homeostasis in the MAM by regulating Ca2+ flux through the Ca2+ channels IP3R and MCU. SFN widens the distance between ER and mitochondria, down-regulates MAM tether protein mitofusin-2, alleviates Ca2+ overload in mitochondria, increases mitochondrial DNA quantities and membrane potential, inhibits ROS production, and enhances mitochondria complexes IV content and ATP synthesis.