Molecular machine used for an different purpose
Many outer membrane proteins contain one or more transmembrane regions. These are areas that span a membrane and thus anchor the protein. The integration of these proteins is often carried out by a special molecular machine. In baker’s yeast this is the MIM complex, which also sits in the outer membrane. “We have now been able to show that this MIM complex also carries out another task,” explains Prof. Dr. Thomas Becker, Director of the Institute of Biochemistry and Molecular Biology at University Hospital Bonn (UKB) and member of the Transdisciplinary Research Area “Life & Health” at the University of Bonn. It appears to be able to influence the number of lipid droplets in the cell. Lipid droplets are fat storages in the cells.”
Becker’s team discovered this previously unknown mechanism in baker’s yeast in cooperation with the research groups of Prof. Dr. Nikolaus Pfanner from the University of Freiburg and Prof. Dr. Maria Bohnert from the University of Münster.
Pfanner is a founding member of the Cluster of Excellence CIBSS – Centre for Integrative Biological Signalling Studies at the University of Freiburg and has made fundamental contributions to our understanding of the development and structure of mitochondria.
A key role in this newly discovered process plays an enzyme known as Ayr1. Similar to the outer membrane proteins, Ayr1 can bind to the MIM complex. Unlike these, however, it is not then integrated into the membrane. “It lacks the transmembrane domain for this,” explains Becker. Instead, it remains bound to the MIM complex.
Ayr1 plays an important role in the lipid metabolism; it thus interacts with the lipid droplets present in the cell. Due to its binding to the MIM complex, the attachment of lipid droplets to the outer membrane of the mitochondria increases. “This also has an impact on the number of lipid droplets,” says Becker. “The more Ayr1 molecules dock onto the MIM complex, the more lipid droplets accumulate in the cell. The binding of Ayr1 changes the function of the MIM complex to such an extent that MIM modulates the number of lipid droplets and thus the cellular lipid metabolism.”
Mechanisms could also exist in humans
This mechanism has so far exclusively been found in baker’s yeast. However, human mitochondria also possess a molecular machinery which integrates proteins into their outer membrane. In human cells, there are also proteins from the same family to which Ayr1 belongs.
“It is thus possible that the number of lipid droplets in our cells is regulated in a similar manner as in single-cell organisms,” explains Thomas Becker, who is also the spokesperson of the Priority Program SPP2453 “Integration of mitochondria into the cellular proteostasis network” and project leader in the Collaborative Research Centre SFB1218 “Mitochondrial regulation of cellular function.” Further studies must now show to what extent similar mechanisms exist in human cells and possibly play a role in the development of metabolic disorders.
