In Caenorhabditis elegans, fasting induces the lysosomal compartment to expand; however, the molecular and cellular mechanisms for this stress response remain largely unclear. In this paper, Tao Xu, Zheng-xing Wu and colleagues show that short-term fasting leads to increased accumulation of polar lipids in lysosomes, and the fasting response is co-ordinately regulated by EGL-4, the C. elegans PKG (protein kinase G) orthologue, and nuclear hormone receptor NHR-49. Their results reveal a new mechanism for lysosomal lipid metabolism during the stress response, which may provide new clues for investigations of lysosome function in energy homoeostasis.
SM (squalene mono-oxygenase) catalyses the first oxygenation step in cholesterol synthesis, immediately before the formation of the steroid backbone at lanosterol. SM provides an important control point in the pathway, and is regulated post-translationally by accelerated cholesterol-dependent ubiquitination and proteasomal degradation. In this paper, Andrew Brown and colleagues show that SM is stabilized by unsaturated fatty acids, which blunt its polyubiquitination by the E3 ubiquitin ligase MARCH6.
In their exploration of possible alternative pathways for bile acid synthesis, in this paper Kaija Autio and colleagues have performed a bile acid analysis of wild-type, Mfe-1-/-, Amacr-/- and Amacr-/-Mfe-1-/- mouse models to show that peroxisomal multifunctional enzyme 1 can participate in bile acid synthesis in both AMACR (α-methylacyl-CoA racemase)-dependent and AMACR-independent pathways.
Toxic lipofuscin in the RPE (retinal pigment epithelium) is implicated in blindness in age-related macular degeneration or recessive Stargardt's disease patients. In this paper, Yalin Wu and colleagues have identified a novel by-product of retinal metabolism called 'pdA2E' in the lipofuscin of the RPE. Characterization of the photoisomerization and oxidation properties of pdA2E have enabled them to propose a non-enzymatic mechanism for its formation in the retina.