A giant named MIMAS in the cellular powerhouses

Mitochondria provide the majority of the body’s energy supply and are therefore regarded as the cellular powerhouses. This energy is sourced from cellular respiration, in which metabolites are burnt in the inner mitochondrial membrane. Mitochondria also play an important role in cellular metabolism, both in the breakdown and synthesis of numerous building blocks of the cell. Many of these processes depend on proteins in the inner membrane that has an extraordinarily high protein density. Defects in these proteins lead to serious diseases in humans. A team led by Dr Heike Rampelt and Prof. Dr Nikolaus Pfanner from the Institute of Biochemistry and Molecular Biology at the University of Freiburg has now discovered a new mega-protein complex with surprising properties in the inner mitochondrial membrane. Their findings were recently published in the scientific journal Cell Reports.

Like assembly-line workers

The new complex is called MIMAS (mitochondrial multifunctional assembly); it is named after a giant in Greek mythology because of its unusual size. It integrates numerous different processes into a common platform, thus deviating from the previous paradigm that the components of a protein complex typically fulfil a common function.

As the research team around first authors Patrick Horten and Dr. Kuo Song was able to show, MIMAS combines very different functions in contrast to the established mitochondrial protein complexes. It comprises numerous factors that consecutively construct the respiratory chain complexes like specialized assembly line workers, but also a variety of transport proteins that transfer ions or metabolites between mitochondria and the rest of the cell, as well as enzymes functioning in energy metabolism and membrane lipid synthesis.

Astounding functional diversity

This astonishing functional diversity in MIMAS is not the only peculiarity of the complex: its stability also depends on a specific membrane lipid whose synthesis enzyme is itself a MIMAS component. These observations suggest that MIMAS is the founder of a novel organising principle in the inner mitochondrial membrane. Proteins with different functions are organised in a megacomplex which could be an important regulatory target, for example in metabolic adaption or pathological changes.

Overview of facts:

• Original Publication: Horten, P., Song, K., Garlich, J., Hardt, R., Colina-Tenorio, L., Horvath, S.E., Schulte, U., Fakler, B., van der Laan, M., Becker, T., Stuart, R.A., Pfanner, N., Rampelt, H.: Identification of MIMAS, a multifunctional mega-assembly integrating metabolic and respiratory biogenesis factors of mitochondria. In: Cell Reports 43, 113772.
  DOI: 10.1016/j.celrep.2024.113772.
  Preview article about the study: Tokatlidis, K.: MIMAS is a new giant multifunctional player in the mitochondrial megacomplex playground. In: Cell Reports 43, 113874.
  DOI: 10.1016/j.celrep.2024.113874
• The study was carried out in collaboration with the working groups of Dr Uwe Schulte and Prof. Dr Bernd Fakler from the University of Freiburg, Prof. Dr Rosemary A. Stuart from Marquette University in Milwaukee, WI, US, Prof. Dr Thomas Becker from the University of Bonn and Prof. Dr Martin van der Laan from Saarland University in Homburg. The research work involved numerous biochemical methods and mass spectrometric analyses.
• Dr Heike Rampelt and Prof. Dr Nikolaus Pfanner lead research groups at the Institute of Biochemistry and Molecular Biology at the Faculty of Medicine, Dr Uwe Schulte and Prof. Dr Bernd Fakler at the Institute of Physiology at the University of Freiburg. They all conduct research at the Freiburg Cluster of Excellence CIBSS in the field of biological signalling research.
• The study was funded by the German Research Foundation (DFG) and the Cluster of Excellence CIBSS at the University of Freiburg.

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