Chaperone-mediated autophagy and endosomal microautophagy: Jointed by a chaperone

Tekirdağ, Kumsal Ayşe; Cuervo, Ana María

doi:10.1074/jbc.r117.818237

Cited by 270 publications

(239 citation statements)

References 98 publications

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“…The endocytic and exocytic pathways interact with the macroautophagic pathway, creating amphisomes through the fusion of multivesicular bodies or late endosomes (LEs) with autophagosomes (Xilouri et al . ; Tekirdag and Cuervo ). There is also an interaction of these pathways with microautophagy, in particular eMI.…”

Section: Intracellular Protein Degradation Systemsmentioning

confidence: 99%

“…Lysosomal hsc70 and other lysosomal proteins regulate this process; in fact, lysosomal hsc70 is essential for this process, and only hsc70-positive lysosomes are capable of CMA. The endocytic and exocytic pathways interact with the macroautophagic pathway, creating amphisomes through the fusion of multivesicular bodies or late endosomes (LEs) with autophagosomes (Xilouri et al 2016b;Tekirdag and Cuervo 2018). There is also an interaction of these pathways with microautophagy, in particular eMI.…”

Section: Intracellular Protein Degradation Systemsmentioning

confidence: 99%

See 1 more Smart Citation

How is alpha‐synuclein cleared from the cell?

Stefanis

Emmanouilidou

Pantazopoulou

et al. 2019

Journal of Neurochemistry

126

112

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The levels and conformers of alpha‐synuclein are critical in the pathogenesis of Parkinson's Disease and related synucleinopathies. Homeostatic mechanisms in protein degradation and secretion have been identified as regulators of alpha‐synuclein at different stages of its intracellular trafficking and transcellular propagation. Here we review pathways involved in the removal of various forms of alpha‐synuclein from both the intracellular and extracellular environment. Proteasomes and lysosomes are likely to play complementary roles in the removal of intracellular alpha‐synuclein species, in a manner that depends on alpha‐synuclein post‐translational modifications. Extracellular alpha‐synuclein is cleared by extracellular proteolytic enzymes, or taken up by neighboring cells, especially microglia and astrocytes, and degraded within lysosomes. Exosomes, on the other hand, represent a vehicle for egress of excess burden of the intracellular protein, potentially contributing to the transfer of alpha‐synuclein between cells. Dysfunction in any one of these clearance mechanisms, or a combination thereof, may be involved in the initiation or progression of Parkinson's disease, whereas targeting these pathways may offer an opportunity for therapeutic intervention. This article is part of the Special Issue “Synuclein”.

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Section: Intracellular Protein Degradation Systemsmentioning

confidence: 99%

Section: Intracellular Protein Degradation Systemsmentioning

confidence: 99%

How is alpha‐synuclein cleared from the cell?

Stefanis

Emmanouilidou

Pantazopoulou

et al. 2019

Journal of Neurochemistry

126

112

View full text Add to dashboard Cite

show abstract

“…LAMP2A forms a multimeric cluster which translocates the cargo across the lysosomal membrane. In the lysosomal lumen, an isoform of HSPA8 binds to the cargo, retaining it within the lysosome and allowing its degradation by hydrolases [89]. Consequently, CMA does not involve the formation of vesicular structures.…”

Section: The Autophagic Processesmentioning

confidence: 99%

Lysosomal Exocytosis, Exosome Release and Secretory Autophagy: The Autophagic- and Endo-Lysosomal Systems Go Extracellular

Buratta

Tancini

Sagini

et al. 2020

IJMS

245

204

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Beyond the consolidated role in degrading and recycling cellular waste, the autophagic-and endo-lysosomal systems play a crucial role in extracellular release pathways. Lysosomal exocytosis is a process leading to the secretion of lysosomal content upon lysosome fusion with plasma membrane and is an important mechanism of cellular clearance, necessary to maintain cell fitness. Exosomes are a class of extracellular vesicles originating from the inward budding of the membrane of late endosomes, which may not fuse with lysosomes but be released extracellularly upon exocytosis. In addition to garbage disposal tools, they are now considered a cell-to-cell communication mechanism. Autophagy is a cellular process leading to sequestration of cytosolic cargoes for their degradation within lysosomes. However, the autophagic machinery is also involved in unconventional protein secretion and autophagy-dependent secretion, which are fundamental mechanisms for toxic protein disposal, immune signalling and pathogen surveillance. These cellular processes underline the crosstalk between the autophagic and the endosomal system and indicate an intersection between degradative and secretory functions. Further, they suggest that the molecular mechanisms underlying fusion, either with lysosomes or plasma membrane, are key determinants to maintain cell homeostasis upon stressing stimuli. When they fail, the accumulation of undigested substrates leads to pathological consequences, as indicated by the involvement of autophagic and lysosomal alteration in human diseases, namely lysosomal storage disorders, age-related neurodegenerative diseases and cancer. In this paper, we reviewed the current knowledge on the functional role of extracellular release pathways involving lysosomes and the autophagic-and endo-lysosomal systems, evaluating their implication in health and disease.

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“…PS flipping is also known to enhance membrane curvature and negative charge required for vesicular transport and protein translocation (43,44). Earlier researchers have also reported that cytosolic proteins like GAPDH are recruited to LEs via microautophagy and to lysosomes via CMA (45)(46)(47)(48)(49). However, CMA-mediated delivery into lysosomes would involve unfolding and degradation of GAPDH while cells transport intact and enzymatically active GAPDH onto their surface and into the ECM, a process that is enhanced upon cellular iron depletion (17)(18)(19).…”

Section: Trafficking Of Gapdh To the Pm Involves Recruitment Into Rapmentioning

confidence: 99%

Trafficking of a multifunctional protein by endosomal microautophagy: linking two independent unconventional secretory pathways

et al. 2019

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During physiologic stresses, like micronutrient starvation, infection, and cancer, the cytosolic moonlighting protein glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) is trafficked to the plasma membrane (PM) and extracellular milieu (ECM). Our work demonstrates that GAPDH mobilized to the PM, and the ECM does not utilize the classic endoplasmic reticulum–Golgi route of secretion; instead, it is first selectively translocated into early and late endosomes from the cytosol via microautophagy. GAPDH recruited to this common entry point is subsequently delivered into multivesicular bodies, leading to its membrane trafficking through secretion via exosomes and secretory lysosomes. We present evidence that both pathways of GAPDH membrane trafficking are up‐regulated upon iron starvation, potentially by mobilization of intracellular calcium. These pathways also play a role in clearance of misfolded intracellular polypeptide aggregates. Our findings suggest that cells build in redundancy for vital cellular pathways to maintain micronutrient homeostasis and prevent buildup of toxic intracellular misfolded protein refuse.—Chauhan, A. S., Kumar, M., Chaudhary, S., Dhiman, A., Patidar, A., Jakhar, P., Jaswal, P., Sharma, K., Sheokand, N., Malhotra, H., Raje, C. I., Raje. M. Trafficking of a multifunctional protein by endosomal microautophagy: linking two independent unconventional secretory pathways. FASEB J. 33, 5626–5640 (2019). http://www.fasebj.org

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Chaperone-mediated autophagy and endosomal microautophagy: Jointed by a chaperone

Cited by 270 publications

References 98 publications

How is alpha‐synuclein cleared from the cell?

How is alpha‐synuclein cleared from the cell?

Lysosomal Exocytosis, Exosome Release and Secretory Autophagy: The Autophagic- and Endo-Lysosomal Systems Go Extracellular

Trafficking of a multifunctional protein by endosomal microautophagy: linking two independent unconventional secretory pathways

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