exchange of glucose and lactate between photoreceptors and the retinal pigment epithelium.

Photoreceptors in the retina of a vertebrate's eye are supported by a tissue adjacent to the retina, the retinal pigment epithelium (RPE). The RPE delivers glucose to the outer retina, consumes photoreceptor outer segments discs, and regenerates 11-cis-retinal. Here we address the question of whether photoreceptors also provide metabolic support to the RPE.

How crosstalk between mitochondria, lysosomes, and other organelles can prevent or promote dry age-related macular degeneration.

Organelles such as mitochondria, lysosomes, peroxisomes, and the endoplasmic reticulum form highly dynamic cellular networks and exchange information through sites of physical contact. While each organelle performs unique functions, this inter-organelle crosstalk helps maintain cell homeostasis. Age-related macular degeneration (AMD) is a devastating blinding disease strongly associated with mitochondrial dysfunction, oxidative stress, and decreased clearance of cellular debris in the retinal pigment epithelium (RPE).

Investigating the consequences of chronic short sleep for metabolism and survival of oxidative stress.

In previous work, we found that short sleep caused sensitivity to oxidative stress; here we set out to characterize the physiological state of a diverse group of chronically short-sleeping mutants during hyperoxia as an acute oxidative stress. Using RNA-sequencing analysis, we found that short-sleeping mutants had a normal transcriptional oxidative stress response relative to controls. In both short-sleeping mutants and controls, hyperoxia led to downregulation of glycolytic genes and upregulation of genes involved in fatty acid metabolism, reminiscent of metabolic shifts during sleep.

Structural basis for growth factor and nutrient signal integration on the lysosomal membrane by mTORC1.

Mechanistic target of rapamycin complex 1 (mTORC1), which consists of mTOR, Raptor, and mLST8, receives signaling inputs from growth factor signals and nutrients. These signals are mediated by the Rheb and Rag small GTPases, respectively, which activate mTORC1 on the cytosolic face of the lysosome membrane. We biochemically reconstituted the activation of mTORC1 on membranes by physiological submicromolar concentrations of Rheb, Rags, and Ragulator.