Researchershave developed a three-dimensional structure.

It allows them to see how and where disease mutations on the twinkle protein can lead to mitochondrial diseases.

The protein is involved in helping cells use energy our bodies convert from food.

Mitochondrial diseases are a group of inherited conditions that affect 1 in 5,000 people and have very few treatments.

The new findings will be particularly relevant for developing targeted treatments for patients who suffer from mitochondrial diseases.

Scientists accurately map clinically relevant variants in the twinkle helicase, the enzyme that unwinds the mitochondrial DNA double helix.

The twinkle structure and all the coordinates are now available in the open data Protein Data Bank.

The researchers used cryo-electron microscopy (CryoEM), which allowed them to see inside the protein.

Mitochondriaare especially vulnerable to mutations.

mtDNA mutations can disrupt their ability to generate energy efficiently for the cell.

Unlike other specialized structures in cells, mitochondria have their own DNA.

In a cell's nucleus there are two copies of each chromosome.

Having a high number of mitochondrial chromosomes allows the cell to tolerate a few mutations.

But accumulation of too many mutated copies leads to mitochondrial disease.

The researchers used a clinical mutation, W315L, known to cause progressive external ophthalmoplegia, to solve the structure.

Using CryoEM, they were able to observe thousands of protein particles appearing in different orientations.

The final structure shows a multi-protein circular arrangement.

They also used mass spectrometry to verify the structure and then did computer simulations to understand why the mutation results in disease.