Heat Shock Protein 70.1 (Hsp70.1) Affects Neuronal Cell Fate by Regulating Lysosomal Acid Sphingomyelinase

Zhu, Hong; Yoshimoto, Tanihiro; Yamashima, Tetsumori

doi:10.1074/jbc.m114.560334

Cited by 37 publications

(34 citation statements)

References 46 publications

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“…Structural integrity of lysosomes is preserved by cytoprotective factors such as HSP70 (that prevents accumulation of the endogenous lysosomotropic sphingolipid sphingosine), lysosomal pools of cholesterol, and Bcl-2 (Johansson et al, 2010). Recently, HSP70.1 has been described to affect the neuronal cell fate by regulating the lysosomal aSMase which plays a cytoprotective role (Zhu et al, 2014). Moreover, cell sensitivity to cisplatin has been related to the acidic lysosomal pH which affects the intracellular drug distribution and the consequent interaction with subcellular targets Sancho-Martinez et al, 2012).…”

Section: Interactions Of Platinum Compounds With the Endo-lysosomal Cmentioning

confidence: 99%

New mechanisms for old drugs: Insights into DNA-unrelated effects of platinum compounds and drug resistance determinants

Gatti

Cassinelli

Zaffaroni

et al. 2015

Drug Resistance Updates

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Section: Interactions Of Platinum Compounds With the Endo-lysosomal Cmentioning

confidence: 99%

New mechanisms for old drugs: Insights into DNA-unrelated effects of platinum compounds and drug resistance determinants

Gatti

Cassinelli

Zaffaroni

et al. 2015

Drug Resistance Updates

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“…Calpain has been implicated in lysosomal destabilization; its cleavage of essential lysosomal membrane proteins such as LAMP2 induces LMP after glucose deprivation in neuronal cells and in a mouse model of light‐induced retinal degeneration . Calpain‐mediated neuronal cell death can be observed after selective cleavage of the chaperone Hsp70 . In these conditions, calpain inhibition protects against cell death both in vitro and in vivo.…”

Section: Lysosomes and Lmp In Other Cell Death Modalitiesmentioning

confidence: 99%

Lysosomal membrane permeabilization and cell death

Wang

Gómez‐Sintes

Boya

2018

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Lysosomes are membrane-enclosed organelles that mediate the intracellular degradation of macromolecules. They play an essential role in calcium regulation and have emerged as key signaling hubs in controlling the nutrient response. Maintaining lysosomal integrity and function is therefore crucial for cellular homeostasis. Different forms of stress can induce lysosomal membrane permeabilization (LMP), resulting in the translocation to the cytoplasm of intralysosomal components, such as cathepsins, inducing lysosomal-dependent cell death (LDCD). Here, we review recent advances that have furthered our understanding of the molecular mechanisms of LMP and the methods used to detect it. We discuss several endolysosomal damage-response mechanisms that mediate the repair or elimination of compromised lysosomes and summarize the role of LMP and cathepsins in LDCD and other cell death pathways. Finally, with the emergence of lysosomes as promising therapeutic targets for several human diseases, we review a variety of therapeutic strategies that seek to either destabilize lysosomes or to maintain, enhance or restore lysosomal function.

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“…The 'calpaincathepsin hypothesis' corroborated the role of lysosomal rupture as an executor of programmed neuronal necrosis after transient brain ischemia in the non-human primates [12,14,[37][38][39][40][41][42][43][44]. During ischemia, excessive Ca 2+ mobilization occurs specifically in the CA1 neuron, and μ-calpain is remarkably activated.…”

Section: +mentioning

confidence: 70%