Lysosomes articles from across Nature Portfolio

Daly, Danson and colleagues employ a multi-omic approach in neuroglioma cells to characterise endolysosomal dysfunction caused by perturbation of the evolutionarily conserved Retromer complex, highlighting Retromer’s neuroprotective function.

Phospholipase D3 polymorphisms are linked to late-onset Alzheimer’s disease but the mechanisms are not understood. Van Acker and colleagues show that Phospholipase D3 processes mitochondrial DNA in lysosomes to maintain lysosomal homeostasis and proper degradation of the amyloid precursor protein.

Mutations in glucocerebrosidase (GCase) cause the lysosomal storage disorder Gaucher’s disease and are the most common risk factor for Parkinson’s disease. Using a fusion protein comprising GCase and a transferrin receptor antibody fragment, the authors show that the transferrin receptor pathway can be therapeutically exploited to both pass the blood-brain barrier and efficiently target lysosomal GCase deficiency.

Yan et al. harness genome-wide CRISPR screens and identify ILF3 as a signalling intermediate negatively regulating mTORC1 activation upon amino acid sensing. ILF3 recruits GATOR2 to tether the GATOR complexes to lysosomes and regulate mTORC1 activity.

ATP13A2 is a lysosomal polyamine transporter, mutated in several diseases including juvenile-onset Parkinson’s disease. Here, the authors report structures of human ATP13A2 in six distinct intermediate states, illustrating most of its conformational cycle.

Bhattacharya et al. describe a TFEB-independent lysosome membrane regeneration pathway that depends on TBC1D15, which stabilizes autophagic lysosomal reformation proteins, potentiating the formation of lysosomal tubules and dynamin-2-dependent scission.