Functional Organisation of Biomembranes

Mechanism for the mutual regulation of Isc1 and Pgc1 phospholipases. Two lipids, diacylglycerol (DAG) and phosphatidylglycerol (PG), inhibit the key enzymes of mitochondrial phospholipid biosynthesis: (i) the PG-phosphate synthase Pgs1, (ii) the phosphatidylserine (PS) decarboxylase Psd1, and (iii) the inositol phosphosphingolipid phospholipase C Isc1. The latter is of particular importance because ceramide, a product of Isc1-catalyzed hydrolysis, inhibits the PG-specific phospholipase C Pgc1, which degrades PG to form DAG. The entire loop ensures the efficient control of PG (cardiolipin) and phosphatidylethanolamine (PE) synthesis in the context of environmental stress stimuli affecting the sphingolipid biosynthetic pathway. OMM – outer mitochondrial membrane; IMM – inner mitochondrial membrane; IPC – inositol phosphoceramide.

The plasma membrane microdomain protein Nce102 contributes to the regulation of sphingolipid metabolism. (A) Synthesis of sphingolipids, important structural and signalling molecules, was inhibited by the addition of myriocin at time t = 0 min. As the yeast cells grew and divided, the punctate pattern typical for Nce102-GFP was lost in the mother cells due to lowering of sphingolipid content. In the daughter cells, Nce102-GFP remained distributed uniformly and did not localize to microdomains. Scale bar: 5 μm. (B) Deletion of the NCE102 gene resulted in changes in the level of sphingolipid classes. In the absence of Nce102 the cellular amount of long-chain bases (PHS, DHS) decreased. On the other hand, phytoceramide (PhytoCer) levels were generally increased. Some complex sphingolipids (IPC and MIPC) were increased, some decreased. LFC: log 2 fold change relative to wild type cells.