Project description:Lysosomes are cytoplasmic organelles that are central for the degradation of macromolecules to maintain cellular homeostasis and health. Here, we discovered an adaptive lysosomal transcriptional response that we termed the lysosomal stress response (LySR). Typified by the induction of a large group of transcripts involved in lysosomal function and proteolysis, the LySR can be triggered by silencing of specific vacuolar H+-ATPase subunits in Caenorhabditis elegans. Notably, LySR activation enhances the clearance of protein aggregates in worm models of Alzheimer's and Huntington’s disease and amyotrophic lateral sclerosis, thereby boosting fitness and extending lifespan, a response that is controlled by the GATA transcription factor, ELT-2. Activating the LySR pathway may therefore represent an attractive mechanism to reduce protein aggregation and, as such, extend healthspan.
Project description:Lysosomes are cytoplasmic organelles that are central for the degradation of macromolecules to maintain cellular homeostasis and health. Here, we discovered an adaptive lysosomal transcriptional response that we termed the lysosomal stress response (LySR). Typified by the induction of a large group of transcripts involved in lysosomal function and proteolysis, the LySR can be triggered by silencing of specific vacuolar H+-ATPase subunits in Caenorhabditis elegans. Notably, LySR activation enhances the clearance of protein aggregates in worm models of Alzheimer's and Huntington’s disease and amyotrophic lateral sclerosis, thereby boosting fitness and extending lifespan, a response that is controlled by the GATA transcription factor, ELT-2. Activating the LySR pathway may therefore represent an attractive mechanism to reduce protein aggregation and, as such, extend healthspan.
