Controlling the cell’s batteries

Mitochondria might have their own DNA, but mutations in the nucleus change how they use their genes.

Image credit: Davide Bonazzi (CC BY 4.0)

Mitochondria are like the batteries of our cells; they perform the essential task of turning nutrients into chemical energy. A cell relies on its mitochondria for its survival, but they are not completely under the cell’s control. Mitochondria have their own DNA, separate from the cell’s DNA which is stored in the nucleus. It contains a handful of genes, which carry the code for some of the important proteins needed for energy production.

These proteins are made in the mitochondria themselves, and their levels are tweaked to meet the cell's current energy needs. To do this, mitochondria make copies of their genes and feed these copies into their own protein-production machinery. By controlling the number of gene copies they make, mitochondria can control the amount of protein they produce. But the process has several steps. The copies come in the form of a DNA-like molecule called RNA and, at first, they contain several genes connected one after the other. To access each gene, the mitochondria need to cut them up. They then process the fragments, fine-tuning the number of copies of each gene. This process – called gene expression – happens in the mitochondria, but they cannot do it on their own; they need proteins that are coded within the DNA in the cell nucleus.

Genes in the cell nucleus can affect gene expression in the mitochondria, changing the cell's energy supply. Scientists do not yet know all of the genes involved, or how this might differ between different tissues or among different individuals. To find out, Ali et al. examined more than 11,000 records of RNA sequences from 36 different human cells and tissues, including blood, fat and skin. This revealed a large amount of variation in the expression of mitochondrial genes. The way the mitochondria processed their genes changed in different cells and in different people. To find out which genes in the nucleus were responsible for the differences in the mitochondria, the next step was to compare RNA levels from the mitochondria to the DNA sequences in the nucleus. This is because changes in the DNA sequence between different people – called genetic variants – can also affect how genes work, and how genes are expressed. This comparison revealed 64 genetic variants from DNA in the cell nucleus that are associated with the expression of genes in the mitochondria. Some of these had a known link to genetic variants involved in diseases like the skin condition vitiligo or high blood pressure.

So, although mitochondria contain their own DNA, they rely on genes from the cell nucleus to function. Changes to the genes in the nucleus can alter the way that the mitochondria process their own genetic code. Understanding how these two sets of genes interact could reveal how and why mitochondria go wrong. This could aid in future research into illnesses like heart disease and cancer.