Hypoxic stress activates chaperone-mediated autophagy and modulates neuronal cell survival

Dohi, Eisuke; Tanaka, Shigeru; Seki, Takahiro; Miyagi, Tatsuhiro; Hide, Izumi; Takahashi, Tetsuya; Matsumoto, Masayasu; Sakai, Norio

doi:10.1016/j.neuint.2012.01.020

Cited by 106 publications

(87 citation statements)

References 49 publications

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“…We also demonstrated that hypoxia increased LAMP2A expression in two cancer cell lines, which is consistent with a previous report that hypoxia increases LAMP2A expression in neural tissue (43). Another recent report demonstrated increased expression of several genes encoding lysosomal components in hypoxic mouse fibroblasts (44).…”

Section: Discussionsupporting

confidence: 93%

Chaperone-mediated Autophagy Targets Hypoxia-inducible Factor-1α (HIF-1α) for Lysosomal Degradation

Hubbi

Kshitiz

et al. 2013

Journal of Biological Chemistry

213

182

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Background: Regulation of hypoxia-inducible factor-1 (HIF-1) is focused on proteasomal degradation of the HIF-1␣ subunit. Results: Pharmacological and genetic approaches establish that HIF-1␣ binds to effectors of chaperone-mediated autophagy (CMA) and is targeted for lysosomal degradation. Conclusion: CMA targets HIF-1␣ for lysosomal degradation. Significance: Lysosomal degradation of HIF-1␣ represents a novel mechanism of HIF-1 regulation and a potential therapeutic target.

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Section: Discussionsupporting

confidence: 93%

Chaperone-mediated Autophagy Targets Hypoxia-inducible Factor-1α (HIF-1α) for Lysosomal Degradation

Hubbi

Kshitiz

et al. 2013

Journal of Biological Chemistry

213

182

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“…Activation of CMA has also been shown to support survival of retinal cells upon activation of a pro-apoptotic program in those cells [37]. Recent studies have demonstrated that CMA is activated during hypoxia and this activation is required for cell survival [38]. Although the specific substrates degraded by CMA under these conditions are not fully elucidated, the fact that the hypoxia-inducible factor 1 has been confirmed as a CMA substrate [39] supports a possible regulatory effect of CMA on the intensity and duration of the cellular response to hypoxia.…”

Section: What Are the Physiological Functions Of Cma?mentioning

confidence: 99%

Chaperone-mediated autophagy: roles in disease and aging

2013

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This review focuses on chaperone-mediated autophagy (CMA), one of the proteolytic systems that contributes to degradation of intracellular proteins in lysosomes. CMA substrate proteins are selectively targeted to lysosomes and translocated into the lysosomal lumen through the coordinated action of chaperones located at both sides of the membrane and a dedicated protein translocation complex. The selectivity of CMA permits timed degradation of specific proteins with regulatory purposes supporting a modulatory role for CMA in enzymatic metabolic processes and subsets of the cellular transcriptional program. In addition, CMA contributes to cellular quality control through the removal of damaged or malfunctioning proteins. Here, we describe recent advances in the understanding of the molecular dynamics, regulation and physiology of CMA, and discuss the evidence in support of the contribution of CMA dysfunction to severe human disorders such as neurodegeneration and cancer.

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“…Each brain was removed and post-fixed in the same fixative overnight at 4°C, followed by cryoprotection with 30% sucrose solution. We prepared 14-m-thick sections using a cryostat, thaw-mounted them on MAS-coated glass slides (Matsunami), and stored them at Ϫ80°C until use (22). Each section was air-dried and washed with PBS (pH 7.4).…”

Section: Methodsmentioning

confidence: 99%

A Brain-specific Grb2-associated Regulator of Extracellular Signal-regulated Kinase (Erk)/Mitogen-activated Protein Kinase (MAPK) (GAREM) Subtype, GAREM2, Contributes to Neurite Outgrowth of Neuroblastoma Cells by Regulating Erk Signaling

Taniguchi

Tanaka

Ishii

et al. 2013

Journal of Biological Chemistry

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Background:We previously identified GAREM1 as a downstream adaptor of the EGF receptor. Results: GAREM2 is a brain-specific GAREM subtype that is also tyrosine-phosphorylated and binds Grb2. Conclusion: GAREM2 is a regulator of neurite outgrowth of neuroblastoma cells in the presence of IGF-1. Significance: This study demonstrates the biological function of the GAREM family proteins, including their expression and subcellular localization.

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Hypoxic stress activates chaperone-mediated autophagy and modulates neuronal cell survival

Cited by 106 publications

References 49 publications

Chaperone-mediated Autophagy Targets Hypoxia-inducible Factor-1α (HIF-1α) for Lysosomal Degradation

Chaperone-mediated Autophagy Targets Hypoxia-inducible Factor-1α (HIF-1α) for Lysosomal Degradation

Chaperone-mediated autophagy: roles in disease and aging

A Brain-specific Grb2-associated Regulator of Extracellular Signal-regulated Kinase (Erk)/Mitogen-activated Protein Kinase (MAPK) (GAREM) Subtype, GAREM2, Contributes to Neurite Outgrowth of Neuroblastoma Cells by Regulating Erk Signaling

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