Validation of the Mitochondrial Delivery of Vitamin B1 to Enhance ATP Production Using SH-SY5Y Cells, a Model Neuroblast

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-1, 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 B1 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-1 (MITO-Porter (VB1)) was efficiently accumulated in mitochondria of SH-SY5Y cells. Further studies confirmed that the level of ATP production after the MITO-Porter (VB1) treatment was significantly increased as compared to a control group that was treated with naked vitamin B-1. This study provides the potential for an innovative therapeutic strategy in which the TCA cycle is activated, thus enhancing ATP production. (C) 2021 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.

Automated summary

This study demonstrates the delivery of vitamin B1 to mitochondria to enhance ATP production through activating the TCA cycle; MITO-Porter containing encapsulated vitamin B1 efficiently accumulated in mitochondria of neuroblast model cells; ATP production significantly increased after MITO-Porter (VB1) treatment compared to naked vitamin B1.