Mitochondria have important tasks. They are not only used to generate energy. They also have regulatory functions, because certain enzymes in these organelles can induce programmed cell death to remove old or damaged cells. The mitochondria require many proteins to do this, but they are unable to produce all of them. Traditional protein importation involves huge molecular complexes in the outer membrane. These translocases recognise certain sequences on the protein precursors destined to enter the mitochondria and transport them across the outer membrane. The protein precursors are transported further on to the translocases located in the inner membrane, which have similar functions to those located in the outer membrane.

But what happens with the substances that have to remain in the intermembrane space, for example chaperones of the family of Tim proteins, which help other proteins in the intermembrane space to fold correctly?

In 2004, Chacinska and her colleagues in Prof. Pfanner’s department discovered the enzyme Mia40, which picks up the precursor proteins of the Tim chaperones from the outer membrane. Mia40 recognises a specific signal, which is characteristic of proteins that have to remain in the intermembrane space. This is a short amino acid sequence attached to the sulphur-containing amino acid cysteine. Mia40, which is anchored in the inner mitochondrial membrane, interacts with the Tim proteins via disulphide bonds that are formed by oxidising sulphur (electron withdrawal). Mia40 cannot do this on its own. Once in a reduced state (uptake of electrons), Mia40 is oxidised by the enzyme Erv1, a sulfhydryl oxidase. This step is necessary, because otherwise Mia40 would accumulate and remain inactive. In addition, Erv1 builds a kind of shelter, together with Mia40,” said Chacinska. In this shelter, another connection can be established between the interior of the protein and two cysteines.