Mitochondria dysfunction shown to cause vitamin b imbalance and genetic changes.


Mitochondria are the cellular powerplant and, reliant on nutrient status, it is known that Vitamin B turns mitochondria into cellular builders. Through vitamin B, mitochondria produce substances to make ingredients for genome replication and repair, cell membrane renewal and synthesis of antioxidants.  However, their functions in conjunction with B-vitamins are only starting to be revealed.

Now, a study from researchers University of Helsinki shows that a progressive mitochondrial myopathy leads to shaken vitamin B-metabolism irrespective of nutrient intake. The team state that their results indicate for the first time that the energy-metabolic defect in a cell can shake its B-vitamin balance and lead to genetic changes.  The opensource study is published in the journal Cell Metabolism.

Previous studies show that mitochondrial disorders are caused by defects in either mitochondrial DNA (mtDNA) encoding 13 proteins of oxidative phosphorylation or, in the 1,300 nuclear genes, encoding mitochondrion-targeted proteins.  The disorders show variable phenotypes ranging from infantile multi-tissue disorders to adult-onset progressive degeneration of the heart, muscle, brain, or sensory organs.  Research shows that this mitochondrial dysfunction affects cellular energy metabolism, however, less is known about the consequences for cytoplasmic biosynthetic reactions.  The current study shows mtDNA replication disorders caused by TWINKLE mutations, namely mitochondrial myopathy and infantile onset spinocerebellar ataxia, remodel cellular deoxynucleotide (dNTP) pools in mice.

The current study shows that mtDNA maintenance disease results in whole cellular nucleotide imbalance. Results show this is associated with widespread changes in cytoplasmic anabolic pathways and a aberrant methyl cycle with deficient metabolite methylation.  The lab state that these results are important for disorders with primary or secondary mtDNA instability and offer targets for metabolic therapy.

The team surmise that their findings show metabolic imbalance in a cell can cause a vitamin metabolic imbalance, irrespective of nutrient intake, and contribute to disease progression.  For the future, the researchers state that this information opens new routes in the search for treatment, especially concerning specific forms of B-vitamins as specific modifiers of metabolic routes.

Source: University of Helsinki

 

Dysfunction of cellular powerplant shakes B-vitamin metabolism and causes genetic damage - healthinnovations

 

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