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Regulation of Autophagy in Health and Disease

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Toxicity and Autophagy in Neurodegenerative Disorders

Part of the book series: Current Topics in Neurotoxicity ((Current Topics Neurotoxicity,volume 9))

Abstract

Macroautophagy (autopagy herein) is a cellular stress mechanism characterized by the engulfment of portions of cytoplasm, proteins and organelles in double or multimembrane vesicles. Cargo carried in these autophagic vesicles are then delivered and subsequently degraded by lysosomal/vacuolar systems. Autophagy occurs at low basal levels in all cell types (from yeast to mammals) under non-deprived conditions, performing homeostatic functions. Under conditions leading to cellular stress such as nutrient or growth factor deprivation, autophagy is activated to provide the cell with intracellular building blocks and substrates for energy generation. In addition to the ubiquitin-proteasome system, autophagy is a major degradation pathway for misfolded, mutant or abnormal proteins. Deregulations and abnormalities of autophagy are deleterious for all cell types including neurons. Consequently, autophagy abnormalities are observed in various neuronal diseases. Here, we summarize the basic autophagy machinery and its regulation, and provide a brief summary of the role of autophagy in healthy neurons and in major neurodegenerative diseases.

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Abbreviations

ATG:

Autophagy related gene

BCL2:

B cell lymphoma 2

CBZ:

Carbamazepine

CMA:

Chaperone mediated autophagy

DETOR DEP:

Domain containing mTOR interacting protein

FAK:

Focal adhesion kinase

Foxo3:

Forkhead box O3

Hsc70:

Heat shock cognate protein 70

Hvps34:

Human vacuolar protein sorting 34

LAMP2a:

Lysosomal associated membrane protein 2 a

LC3:

Microtubule associated protein 1 light chain 3

Mfns:

Mitofusins

Mtorc1/2:

Mammalian Target of Rapamycin Complex 1 and 2

PEN2:

Presenilin enhancer 2

PI3K:

Phosphoinositide 3 kinase

PINK1:

PTEN induced putative kinase1

PS1/2:

Presenilin 1 and 2

Rag Ras:

Related GTP-binding protein

TSC:

Tuberous sclerosis complex

UPS:

Ubiquitin proteasome system

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Acknowledgements

This work was supported by The Scientific and Technological Research Council of Turkey (TUBITAK) 1001 Grant Project Number 110T405 and Sabanci University. D.G. is a recipient of the Turkish Academy of Sciences (TUBA) GEBIP Award and the EMBO Strategical Development and Installation Grant (EMBO-SDIG).

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  1. Faculty of Engineering and Natural Sciences, Molecular Biology Genetics and Bioengineering Program, SABANCI University, 34956, Istanbul, Turkey

    Amal Arachiche & Devrim Gozuacik

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  1. Amal Arachiche
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  2. Devrim Gozuacik
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Correspondence to Devrim Gozuacik .

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  1. Bioquímica y Biología Molecular y Gen., Facultad de Enfermería y T.O., Cáceres, Spain

    José M. Fuentes

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Arachiche, A., Gozuacik, D. (2015). Regulation of Autophagy in Health and Disease. In: Fuentes, J. (eds) Toxicity and Autophagy in Neurodegenerative Disorders. Current Topics in Neurotoxicity, vol 9. Springer, Cham. https://doi.org/10.1007/978-3-319-13939-5_1

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