Mitochondria, the power stations of human cells, provide energy for cellular metabolism. But how these power stations evolved, and how are they constructed, has long been the subject of scientific curiosity.
A new study tackled oxidase assembly machinery (OXA) in the development of the inner membrane of mitochondria and the energy supply of cells and found that this protein complex is essential for the integration of certain proteins into the inner membrane of mitochondria -- proteins that play a role in cellular respiration and other processes.
The imported OXA-dependent proteins play important functions that range from cellular respiration, the exchange of metal ions, and biochemical reactions, to the integration of proteins enabling the transfer of metabolic products across the inner membrane. When the integration or function of these respiratory proteins is blocked, this can cause mitochondrial-based neuromuscular diseases or cancer.
Mitochondria originated from a bacterial precursor, they have their own DNA molecule in which the structure of several proteins is recorded, and an OXA-like machinery already existed in that bacterial precursor and has been conserved throughout evolution.
The proteins produced, according to the mitochondrion's genetic material, are integrated by the OXA into the inner mitochondrial membrane. The genetic information of 99 percent of the proteins comprising mitochondria are stored in the cell's nucleus, however. The cell produces these protein molecules in the cytoplasm, after which the TOM, or "Translocase of the Outer Membrane," and the TIM, "Translocase of the Inner Membrane," transport them across the outer and inner membranes into mitochondria.
Fluorescence microscopy image of the mitochondrial network (left, in green) and the corresponding light microscopy image (right) of a dividing yeast cell. Images: Nils Wiedemann, University of Freiburg
How many of these imported proteins are also integrated into the inner membrane by OXA has been. The researchers systematically searched for proteins integrated by OXA into the inner membrane after they had been imported via TOM and TIM. They used quantitative mass spectrometry to identify mitochondrial inner membrane proteins which are reduced in cells without OXA. By tracing the integration of radioactively labelled proteins into the inner mitochondrial membrane, they were able to prove that OXA is necessary for this process.
Citation: Sebastian B. Stiller, Jan Höpker, Silke Oeljeklaus, Conny Schütze, Sandra G. Schrempp, Jens Vent-Schmidt, Susanne E. Horvath, Ann E. Frazier, Natalia Gebert, Martin van der Laan, Maria Bohnert, Bettina Warscheid, Nikolaus Pfanner, Nils Wiedemann (2016): Mitochondrial OXA Translocase Plays a Major Role in Biogenesis of Inner-Membrane Proteins; Cell Metabolism; DOI: 10.1016/j.cmet.2016.04.005