Dietary zinc deficiency increases damage rate and copy number of mitochondrial DNA in the mouse liver

Abstract

Zinc is an essential trace element involved in many physiological processes, ranging from cellular growth and immune functions to enzymatic activity and gene expression. Inadequate dietary zinc levels can disrupt the functioning of numerous organs, including the liver. Given the pivotal role played by the liver, in-depth understanding of the mechanisms driving disorders in this organ caused by zinc deficiency is of great importance. In the present study, the effects of a four-week low-zinc diet on the integrity and copy number of mitochondrial DNA (mtDNA) in the liver was assessed using a mouse model. The research revealed a significantly elevated damage rate and an increased copy number of mtDNA in the livers of mice subjected to a low-zinc diet when compared to control animals. These findings indicate that a zinc deficiency, by promoting DNA damage in mitochondrial genomes, increases a potential risk of harmful mutations that could compromise ATP production in the liver. The rise in the mtDNA copy number suggests an initial compensatory response to the detrimental effects of the zinc deficiency, which is likely to diminish with a chronic insufficiency of this element. The study confirmed the significant role of mitochondria in the processes leading to liver dysfunction induced by a zinc deficiency. It showed additionally that mtDNA is a very sensitive indicator of the liver's condition that is responsive to environmental changes such as a micronutrient deficiency in the diet.