Three processing steps to lipid biosynthesis
Publication in the Journal of Biological Chemistry: researchers shed light on the biogenesis pathway of a central enzyme of lipid biosynthesis
Cellular “power plant” is an apt metaphor for characterizing the main function of mitochondria. However, mitochondria are also involved in numerous biosynthesis. They play a key role in the generation of phospholipids like phosphatidylethanolamine and cardiolipin.
Phospholipids form the lipid bilayer of the biological membranes surrounding cells and cell organelles. Phosphatidylethanolamine and cardiolipin play a particularly important role for the functions of many membrane-bound proteins and for the dynamics of membranes. An insufficiency of mitochondrial lipid synthesis can thus lead to severe illnesses with an impairment of the immune system and the muscles.
Dr. Thomas Becker
New insight into the biogenesis of the enzyme Psd1
Phosphatidylserine decarboxylase (Psd1) of the mitochondrial inner membrane carries out the synthesis of phosphatidylethanolamine, one of the most common phospholipids of all cell membranes. Errors in the process of maturation and in the activation of the enzyme cause a reduction in the amount of phosphatidylethanolamine in the cell membranes. A Freiburg research team led by BIOSS member Dr. Thomas Becker and the research group of Prof. Dr. Günther Daum at the Graz University of Technology, Austria, have succeeded in gaining fundamental insights into the biogenesis of the enzyme Psd1.
Maturation of the enzyme requires three processing steps
Psd1 is produced as a precursor protein in the cytosol on ribosomes with a mitochondrial signaling sequence. This precursor protein is imported into the mitochondria via protein translocases and integrated into the inner membrane. Within the context of the collaboration between Collaborative Research Center SFB746 and the Cluster of Excellence BIOSS Centre for Biological Signalling Studies, Susanne Horvath from Graz and Lena Böttinger from Thomas Becker’s research group in Freiburg were able to demonstrate that the maturation of this enzyme in the mitochondria requires three processing steps: Two proteases from the mitochondrial matrix remove the recognition sequence one after the other. Then Psd1 cleaves itself at a conserved amino acid sequence. This autoprocessing is the precondition for obtaining enzymatic activity. In this step, the enzymatically active domain is separated from its membrane anchor. However, the interaction of the two Psd1 domains remains intact, enabling the enzyme to synthesize phosphatidylethanolamine. The biogenesis of Psd1 thus requires a surprisingly complex maturation mechanism. These important findings on the generation of active Psd1 have now been published in the renowned Journal of Biological Chemistry.
Significance for regulatory mechanisms
These discoveries give an impression of how complicated the path to an active enzyme in the mitochondrial membrane is. The biogenesis pathway of Psd1 was previously only little understood. The new findings will thus be of prime significance for future studies on the synthesis of phosphotidylethanolamin and its regulatory mechanisms.
Original publication:
Horvath, S.E., Böttinger, L., Vögtle, F.N., Wiedemann, N., Meisinger, C., Becker, T. and Daum, G. (2012)
Processing and topology of the yeast mitochondrial phosphatidylserine decarboxylase 1.
J. Biol. Chem. 287, 36744-36755.