Validation of the Mitochondrial Delivery of Vitamin B 1 to Enhance ATP Production Using SH-SY5Y Cells, a Model Neuroblast

• Published in: Journal of pharmaceutical sciences 2022-02, Vol.111 (2), p.432
• Main Authors: Yamada, Yuma, Ishimaru, Takuya, Ikeda, Kohei, Harashima, Hideyoshi
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate; Drug Delivery Systems; Humans; Mitochondria; Thiamine; Vitamins
• ISSN: 1520-6017
• DOI: 10.1016/j.xphs.2021.08.033

Large amounts of ATP are produced in mitochondria especially in the brain and heart, where energy consumption is high compared with other organs. Thus, a decrease in ATP production in such organs could be a cause of many diseases such as neurodegenerative diseases and heart disease. Based on thus assumption, increasing intracellular ATP production in such organs could be a therapeutic strategy. In this study, we report on the delivery of vitamin B , a coenzyme that activates the tricarboxylic acid (TCA) cycle, to the inside of mitochondria. Since the TCA cycle is responsible for ATP production, we hypothesized delivering vitamin B to mitochondria would enhance ATP production. To accomplish this, we used a mitochondrial targeted liposome a "MITO-Porter" as the carrier. Using SH-SY5Y cells, a model neuroblast, cellular uptake and intracellular localization were analyzed using flow cytometry and confocal laser scanning microscopy. The optimized MITO-Porter containing encapsulated vitamin B (MITO-Porter (VB )) was efficiently accumulated in mitochondria of SH-SY5Y cells. Further studies confirmed that the level of ATP production after the MITO-Porter (VB ) treatment was significantly increased as compared to a control group that was treated with naked vitamin B . This study provides the potential for an innovative therapeutic strategy in which the TCA cycle is activated, thus enhancing ATP production.