First, we study how glucose availability determines the metabolic switch between fermentation and respiration in yeast. When glucose is available, respiration is turned off by a mechanism termed glucose repression. Release from glucose repression depends on the highly conserved metabolic kinase SNF1, which is the homolog of mammalian AMPK. SNF1 activity is regulated by the essential PP1-type protein phosphatase Glc7 and its regulatory subunit Reg1. We have characterized a crosstalk between the cytosolic chaperone Ssb, the 14-3-3 protein Bmh, and the Glc7/Reg1 phosphatase, which fine tunes SNF1 activity.
Second, we investigate various facets of the early steps of protein biogenesis, in which ribosomes, beyond their role in protein synthesis, serve as a hub for downstream processes. As an example, targeting of newly synthesized membrane proteins requires a regulated crosstalk between ribosomes, cytosolic targeting factors, and membrane receptors. The major challenge during membrane protein biogenesis is how to prevent aggregation prior to membrane integration. In the case of ER membrane proteins, this is achieved by highly specific machineries, which mediate co-translational membrane integration. In contrast, mitochondrial membrane proteins reach their destination mainly post-translationally and all-purpose cytosolic chaperones, such as Hsp70 and Hsp90, are thought to shield transmembrane domains during passage through the cytosol. The exact targeting routes of mitochondrial membrane proteins, however, are only poorly understood.
Keywords
Ribosomes, translation, co-translational protein folding, co-translational targeting to the ER, chaperones, ribosome-bound protein biogenesis factors, signaling kinases, regulation of glucose metabolism, AMPK/SNF1, TORC1