Mitochondria, the cells’ so-called powerhouse, are responsible for the energy supply of the organism and perform functions in metabolic and signaling processes. Researchers at the University Hospital Bonn (UKB) and the University of Freiburg have gained systematic insight into the organization of proteins in mitochondria. The protein map of mitochondria represents an important basis for further functional characterization of the cell’s powerhouse and thus has implications for diseases. The study has now been published in the recognized scientific journal Nature.
Mitochondria are among the most important cell compartments. They are bounded organelles surrounded by a double membrane. Mitochondria are considered the powerhouse of the cell as they produce the majority of the energy required for all cellular processes. In addition, they take over many other functions in the metabolism and provide a signaling surface for inflammatory processes and programmed cell death. Defects in mitochondria lead to several diseases, especially in the nervous system. Therefore, the molecular understanding of mitochondrial processes is of the highest relevance for basic medical research. The molecular workers in the cell are usually proteins. Mitochondria can contain about 1,000 or more different proteins. To perform functions, several of these molecules often work together and form a protein machine, also called a protein complex. Proteins also interact in the execution and regulation of molecular processes. Yet little is known about the organization of mitochondrial proteins in such complexes.
Precision in Analysis of Dynamic Protein Machines
The research groups of Prof. Thomas Becker and dr. Fabian den Brave at UKB, together with the research groups of Prof. Bernd Fakler, dr. Uwe Schulte and Prof. Nikolaus Pfanner at the University of Freiburg created a high-resolution image of the organization of proteins in protein complexes, known as MitCOM. This involved a specific method known as complex profiling to record fingerprints of individual proteins with unprecedented resolution. MitCOM reveals the organization into protein complexes of more than 90 percent of the mitochondrial proteins of baker’s yeast. This makes it possible to identify new protein-protein interactions and protein complexes – important information for further studies.
Quality control in mitochondrial entry gate TOM as an example
Researchers at UKB in collaboration with Collaborative Research Center 1218 “Regulation of cellular function by mitochondria” have shown how this data set can be used to elucidate new processes. Mitochondria import 99 percent of their proteins from the liquid part of the cell, known as the cytosol. In this process, a protein machinery called the TOM complex enables the uptake of these proteins through the membrane into the mitochondria. However, it is largely unclear how proteins are removed from the TOM complex when they become stuck during the transport process. To elucidate this, the team led by Prof. Becker and Dr. the Brave information from the MitCOM dataset. It was shown that non-imported proteins are specifically marked for cellular degradation. Research at the Ph.D. student Arushi Gupta further revealed a pathway by which these tagged proteins are subsequently targeted for degradation. Understanding these processes is important because defects in protein import can lead to cellular damage and neurological diseases.
The example from our study shows the great potential of the MitCOM data set to elucidate new mechanisms and pathways. Thus, this map of proteins represents an important source of information for further studies that will help us understand the functions and origins of the cell’s powerhouse.”
Prof. Thomas Becker, director of the Department of Biochemistry and Molecular Biology at UKB
Schulte, U. et al. (2023) Mitochondrial complexome reveals quality control pathways for protein import. Nature. doi.org/10.1038/s41586-022-05641-w.