Expansion of lysosomal capacity in early adult neurons driven by TFEB/HLH-30 protects dendrite maintenance during aging in Caenorhabditis elegans.

ABSTRACT: Lysosomes are essential for neuronal homeostasis, providing degradation and recycling functions necessary to support neurons' complex operations and long lifespans. However, the regulation of lysosomal degradative capacity in healthy neurons is poorly understood. Here, we investigate the role of HLH-30, the sole Caenorhabditis elegans homolog of Transcription Factor EB (TFEB), a master regulator of lysosome biogenesis and autophagy that is thought to predominantly function in the context of starvation or stress. We demonstrate that HLH-30 is dispensable for neuronal development but acts cell-intrinsically to expand lysosomal degradative capacity during early adulthood. Loss of HLH-30 leads to lysosomal dysfunction and delayed turnover of synaptic vesicle proteins from the synapse. Notably,

SUBMITTER: Zhong R 

PROVIDER: S-EPMC12510649 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature