TSC but not PTEN loss in starving cones of retinitis pigmentosa mice leads to an autophagy defect and mTORC1 dissociation from the lysosome.

ABSTRACT: Understanding the mechanisms that contribute to secondary cone photoreceptor loss in retinitis pigmentosa (RP) is critical to devise strategies to prolong vision in this neurodegenerative disease. We previously showed that constitutive activation of the mammalian target of rapamycin complex 1 (mTORC1), by loss of its negative regulator the tuberous sclerosis complex protein 1 (Tsc1; also known as Hamartin), was sufficient to promote robust survival of nutrient-stressed cones in two mouse models of RP by improving glucose uptake and utilization. However, while cone protection remained initially stable for several weeks, eventually cone loss resumed. Here we show that loss of Tsc1 in the cones of RP mice causes a defect in autophagy, leading to the accumulation of ubiquitinated aggregates. W

SUBMITTER: Venkatesh A 

PROVIDER: S-EPMC5108335 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature