New structure found in plain sight

Abstract

Like explorers spotting an uncharted island on the horizon, Imanishi et al. (page 373) have identified a previously unknown cellular structure that could be an entirely new organelle. The structure, located in cells of the retinal pigment epithelium, appears to be an essential waypoint in the retinoid cycle—the series of chemical reactions that regenerates 11-cis-retinal, the chromophore for rhodopsin, after light converts it to all-trans-retinal. Figure Storage sites for retinyl esters called retinosomes (red) do not colocalize with organelles such as the Golgi (blue). Isolated retinas do not survive long outside of the eye, complicating studies of retinal biology. The authors circumvented this problem by looking directly into the eyes of live mice with two-photon fluorescent microscopy. Retinol and retinyl esters show weak intrinsic fluorescence, producing high-resolution images of intact retinal cells and revealing a fence-like intracellular structure dubbed the retinyl ester storage particle, or retinosome. In wild-type mice exposed to light, retinyl ester levels in retinosomes rise, and then fall, consistent with the recycling of retinoid intermediates produced by light exposure. Retinosomes are absent in mice lacking the enzyme LRAT, which produces retinyl esters. Mice lacking RPE65, which is required for processing retinyl esters, accumulate large quantities of the esters in overgrown retinosomes. Biochemical analysis shows that retinosomes also contain adipose differentiation–related protein (ADRP). The new structure provides a context for understanding the retinoid cycle. By compartmentalizing a portion of the cycle, the retinosome can locally enrich intermediates in the cycle to drive energetically unfavorable reactions. Just as important, sequestering the retinyl esters can prevent toxic reaction intermediates from poisoning the cell. The retinosome's highly ordered structure suggests that it incorporates other proteins, and the authors are now trying to use ADRP as a hook to isolate pure retinosomes for further analysis. Since defects in the retinoid cycle underlie many forms of congenital blindness, the ability to observe retinosomes directly in intact eyes may also provide a powerful diagnostic tool in the clinic. ▪