Optineurin tunes outside-in signaling to regulate lysosome biogenesis and phagocytic clearance in the retina.

ABSTRACT: Balancing the competing demands of phagolysosomal degradation and autophagy is a significant challenge for phagocytic tissues. Yet how this plasticity is accomplished in health and disease is poorly understood. In the retina, circadian phagocytosis and degradation of photoreceptor outer segments by the postmitotic retinal pigment epithelium (RPE) are essential for healthy vision. Disrupted autophagy due to mechanistic target of rapamycin (mTOR) overactivation in the RPE is associated with blinding macular degenerations; however, outer segment degradation is unaffected in these diseases, indicating that distinct mechanisms regulate these clearance mechanisms. Here, using advanced imaging and mouse models, we identify optineurin as a key regulator that tunes phagocytosis and lysosomal capaci

SUBMITTER: Tan LX 

PROVIDER: S-EPMC10529777 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature