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New method for delivering an antioxidant directly to mitochondria in the liver, mitigating oxidative stress

Delivery of antioxidants to liver mitochondria
CoQ10-MITO-Porter (green sphere with red and blue protrusions) is taken up by liver cells (hepatocytes) and targets mitochondria. The delivery of CoQ10 reduces the excess ROS produced by mitochondria and thus reduces oxidative stress. Credit: Mitsue Hibino, et al. Scientific Reports. May 10, 2023

Mitochondria are microscopic organelles found within cells, and are by far the largest producer of the molecule adenosine triphosphate (ATP), which provides energy to many processes in living cells. The process by which mitochondria synthesize ATP generates a large amount of reactive oxygen species (ROS), chemical groups that are highly reactive.

In a healthy cell, the ROS are controlled by the mitochondria; however, when this balance is lost, the excess ROS damages the mitochondria and subsequently cells and tissues. This phenomenon, known as , can cause premature aging and disease. The ROS that cause oxidative stress can be controlled by antioxidants.

A research team led by Professor Yuma Yamada, Distinguished Professor Hideyoshi Harashima and Assistant Professor Mitsue Hibino at Hokkaido University have developed a system to deliver antioxidants to mitochondria to mitigate the effects of excess ROS. Their findings have been published in Scientific Reports.

"We previously developed a which we named CoQ10-MITO-Porter," explained Hibino. "This system consists of the antioxidant molecule Coenzyme Q10 (CoQ10)—which is also required by mitochondria for ATP production—encapsulated by a lipid nanoparticle that would target mitochondria. In this study, we aimed to test if this system could work in living organisms."

Delivery of antioxidants to liver mitochondria
Damage to the liver induced by acetaminophen (dotted blue outlines) is almost completely mitigated by CoQ10-MITO-Porter (right), compared to the effect of phosphate buffered saline (left) and direct administration of CoQ10(center). Credit: Mitsue Hibino, et al. Scientific Reports. May 10, 2023

Variations of the formula for the synthesis of CoQ10-MITO-Porter were tested, and their structures were examined with . CoQ10-MITO-Porter was administered to mice models with acetaminophen-induced . Acetaminophen overdoses cause excess ROS in , which in turn damages cells in the . CoQ10-MITO-Porter was transported primarily to the liver and measurably reduced the damage caused by ROS. A further discovery was that downsized CoQ10-MITO-Porter particles with more efficient packaging of CoQ10 were more effective at treating liver damage than the original formulation.

"Our study has shown that the MITO-Porter system we developed can be used to deliver CoQ10 to the liver, making it an important therapeutic strategy against conditions that cause oxidative stress," concluded Yamada. "Our future work will focus on elucidating the mechanism responsible for the therapeutic effect of CoQ10."

More information: Mitsue Hibino et al, A System that Delivers an Antioxidant to Mitochondria for the treatment of Drug-Induced Liver Injury, Scientific Reports (2023). DOI: 10.1038/s41598-023-33893-7.

Journal information: Scientific Reports

Citation: New method for delivering an antioxidant directly to mitochondria in the liver, mitigating oxidative stress (2023, May 10) retrieved 7 June 2023 from
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