Lipids are important as a cellular energy source, signalling molecules and biological building blocks allowing for subcellular compartmentalisation. The maintenance of precise lipid compositions of biological membranes, which largely differ among the different cell organelles, is of remarkable importance to guarantee integrity, proper signalling and trafficking. Fungi can sense and adapt to a diversity of lipid stresses or lipid imbalance via conserved MAPK signalling and the RIM pathway.
In the first part of my talk I will focus on MAPK signalling pathways stimulated by stabilisation of the actin cytoskeleton. I will further show evidence that MAPK activation depends on the mitochondrial voltage dependent anion channel (VDAC), and that it can further trigger programmed cell death. VDAC´s involvement in cellular signalling is however surprising and suggests a mechanism through which the cytoskeleton and mitochondria co-ordinate MAPK signalling and decision-making.
In the second part of my talk I will show that an increase in cellular diacylglycerol (DAG) triggers regulated necrosis, which is controlled by the RIM pathway. The pathway constitutes a signal transduction route, which is primarily known for sensing and reacting to pH alteration. Importantly, it is required for pathogenicity in Candida albicans, Cryptococcus species and other pathogenic fungi. However, the RIM pathway not only senses alkaline conditions, but also recognises lipid alterations in the plasmamembrane or changes within the asymmetrical lipid distribution of its two leaflets. I will present evidence that DAG induced cell death depends on functional RIM signalling, ESCRT trafficking and vacuole/lysosome fusion as part of endosomal recycling. Our data suggest a new conserved cellular lipotoxicity pathway.