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Lysosomes in cell death

Abstract

For many years apoptosis research has focused on caspases and their putative role as sole executioners of programmed cell death. Accumulating information now suggests that lysosomal cathepsins are also pivotally involved in this process, especially in pathological conditions. In particular, the role of lysosomes and lysosomal enzymes in initiation and execution of the apoptotic program has become clear in several models, to the point that the existence of a ‘lysosomal pathway of apoptosis’ is now generally accepted. This pathway of apoptosis can be activated by death receptors, lipid mediators, and photodamage. Lysosomal proteases can be released from the lysosomes into the cytosol, where they contribute to the apoptotic cascade upstream of mitochondria. This review focuses on the players and the molecular mechanisms involved in the lysosomal pathway of apoptosis as well as on the importance of this pathway in development and pathology.

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Abbreviations

CNS:

central nervous system

EPM1:

progressive myoclonus epilepsy

FAN:

factor associated with neutral sphingomyelinase

PLA2:

phospholipase A2

ROS:

reactive oxygen species

TNF-α:

tumor necrosis factor-alpha

TNF-R1:

tumor necrosis factor-receptor 1

TRAIL:

tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)

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Acknowledgements

This work was supported by NIH Grant (DK63947 to G.J.G.), the Palumbo Foundation, and the Mayo Foundation.

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Guicciardi, M., Leist, M. & Gores, G. Lysosomes in cell death. Oncogene 23, 2881–2890 (2004). https://doi.org/10.1038/sj.onc.1207512

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