Acutely damaged lysosomes can regenerate themselves by repurposing damaged membranes. After damage, cytosolic TBC1D15 relocalizes to impaired lysosomes and assembles the autophagic lysosomal reformation machinery to drive this regeneration. This mechanism exemplifies an immediate cellular response to mitigate the crisis of severe lysosomal damage.
This is a preview of subscription content, log in via an institution to check access.
References
Ballabio, A. & Bonifacino, J. S. Lysosomes as dynamic regulators of cell and organismal homeostasis. Nat. Rev. Mol. Cell Biol. 21, 101–118 (2020). This review article describes the involvement of lysosomes in several cellular pathways and diseases.
Skowyra, M. L. et al. Triggered recruitment of ESCRT machinery promotes endolysosomal repair. Science 360, eaar5078 (2018). This paper reports the mechanistic details of lysosomal membrane repair.
Maejima, I. et al. Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury. EMBO J. 32, 2336–2347 (2013). This paper is the first, to our knowledge, to describe the process of lysophagy.
Yu, L. et al. Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature 465, 942–946 (2010). This paper describes ALR after a long period of cell starvation.
Nakamura, S. et al. LC3 lipidation is essential for TFEB activation during the lysosomal damage response to kidney injury. Nat. Cell Biol. 22, 1252–1263 (2020). This paper describes the involvement of lysosomal damage in a model of the kidney disease oxalate crystal-mediated nephropathy.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This is a summary of: Bhattacharya, A. et al. A lysosome membrane regeneration pathway depends on TBC1D15 and autophagic lysosomal reformation proteins. Nat. Cell Biol. https://doi.org/10.1038/s41556-023-01125-9 (2023).
Rights and permissions
About this article
Cite this article
TBC1D15 drives regeneration of acutely damaged lysosomes. Nat Cell Biol 25, 639–640 (2023). https://doi.org/10.1038/s41556-023-01135-7
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41556-023-01135-7
- Springer Nature Limited