Figures
Expansion of lysosomal capacity in early adult neurons driven by TFEB/HLH-30 protects dendrite maintenance during aging in Caenorhabditis elegans
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, Zhong and Richardson 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. The authors 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. Overall, their study establishes a critical role for HLH-30/TFEB in promoting lysosomal capacity to preserve neuronal homeostasis and structural integrity of mature neurons in vivo. The image shows the morphology of the C. elegans PVD neuron in wild-type animals (upper) versus TFEB/hlh-30 loss-of-function mutant animals (lower) in mid-adulthood. In the TFEB/hlh-30 mutant, but not in wild-type, dendrite degeneration and disorganized outgrowths are visible.
Image Credit: Ruiling Zhong and Claire Richardson
Citation: (2025) PLoS Biology Issue Image | Vol. 23(9) October 2025. PLoS Biol 23(9): ev23.i09. https://doi.org/10.1371/image.pbio.v23.i09
Published: October 8, 2025
Copyright: © 2025 . This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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, Zhong and Richardson 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. The authors 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. Overall, their study establishes a critical role for HLH-30/TFEB in promoting lysosomal capacity to preserve neuronal homeostasis and structural integrity of mature neurons in vivo. The image shows the morphology of the C. elegans PVD neuron in wild-type animals (upper) versus TFEB/hlh-30 loss-of-function mutant animals (lower) in mid-adulthood. In the TFEB/hlh-30 mutant, but not in wild-type, dendrite degeneration and disorganized outgrowths are visible.
Image Credit: Ruiling Zhong and Claire Richardson