Quality control in the power plants of the cell

The right amount, the right function: A team of scientists led by Dr. Martin van der Laan has produced new findings on the construction plans of the mitochondria. Mitochondria are network-like structures in cells that supply the energy necessary for life processes by breaking down food components. Inside of them are biological membrane systems that carry out chemical reactions to convert energy. The membrane systems can only perform their tasks well if they receive numerous<br specialized proteins that are produced outside of
the mitochondria. But how does the cell ensure that only fully functional proteins are released into the membranes of the cellular power plants in just the right amounts? This is critical, because errors in the structure of mitochondrial membranes lead to diseases, since muscle and nerve cells can no longer be supplied with sufficient energy. The Freiburg research team has succeeded in answering this question in a study published in the journal . Dr. Raffaele Ieva and Dr. Sandra Schrempp discovered that the protein subunit Mgr2 sorts out defective membrane proteins inside the mitochondria and prevents them from being released into the membrane.

The Freiburg researchers demonstrated the mechanism the cell uses to prevent errors from occurring. The central protein translocase (TIM23) inside the mitochondria contains the subunit Mgr2. It delays the transfer of newly arrived proteins into the mitochondrial membrane system, thus giving the cell time to conduct a careful quality control procedure. Cells that do not contain the molecular gatekeeper Mgr2 are unable to efficiently sort out the defective membrane proteins. However, the uncontrolled release of intact proteins can also cause problems for the mitochondria. “To maintain the structure and function of mitochondria, it is essential for precisely defined amounts of certain proteins to be present,” explains Ieva. “Mgr2 plays an important role in creating this balance.” When Mgr2 is inactive, the mitochondria are split up, says Ieva. This can also be observed in patients with severe neurodegenerative diseases. “Our study contributes to our understanding of the functional architecture of living cells,” says van der Laan. “In the future, the findings could also help scientists to decipher disease mechanisms linked to the dysfunction of the mitochondria.”

The Freiburg scientists in van der Laan’s team conduct their research at the Institute of Biochemistry and Molecular Biology of the University of Freiburg and are members of the Cluster of Excellence BIOSS Centre for Biological Signalling Studies. Van der Laan also heads a subproject of Collaborative Research Center 746 “Functional Specificity by Coupling and Modification of Proteins.” Ieva is a postdoctoral researcher at the Institute of Biochemistry and Molecular Biology of the University of Freiburg. Schrempp is a member of van der Laans research group; the study is part of her doctoral dissertation.

Original publication:

Mgr2 Functions as Lateral Gatekeeper for Preprotein Sorting in the Mitochondria Inner Membrane.R. Ieva, S.G. Schrempp, ?. Opali?ski, F. Wollweber, P. Höß,, A.K. Heißwolf, M. Gebert, Y. Zhang, B. Guiard, S. Rospert, T. Becker, A. Chacinska, N. Pfanner, M. van der Laan. 2014. Molecular Cell, doi: 10.1016/j.molcel.2014.10.010

http://www.sciencedirect.com/science/article/pii/S1097276514007941