Abstract
Autophagy is a lysosomal degradation pathway of eukaryotic cells that is highly conserved from yeast to mammals. During this process, cooperating protein complexes are recruited in a hierarchic order to the phagophore assembly site (PAS) to mediate the elongation and closure of double-membrane vesicles called autophagosomes, which sequester cytosolic components and deliver their content to the endolysosomal system for degradation. As a major cytoprotective mechanism, autophagy plays a key role in the stress response against nutrient starvation, hypoxia, and infections. Although numerous studies reported that impaired function of core autophagy proteins also contributes to the development and progression of various human diseases such as neurodegenerative disorders, cardiovascular and muscle diseases, infections, and different types of cancer, the function of this process in human diseases remains unclear. Evidence often suggests a controversial role for autophagy in the pathomechanisms of these severe disorders. Here, we provide an overview of the molecular mechanisms of autophagy and summarize the recent advances on its function in human health and disease.
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Abbreviations
- AD:
-
Alzheimer’s disease
- ALS:
-
Amyotrophic lateral sclerosis
- ATG:
-
Autophagy related
- CM:
-
Cardiomyopathy
- GAP:
-
GTPase activating protein
- GAS:
-
Group A Streptococcus
- GDP:
-
Guanosine diphosphate
- GEF:
-
Guanosine nucleotide exchange factor
- GTP:
-
Guanosine triphosphate
- HD:
-
Huntington’s disease
- HF:
-
Heart failure
- HIV:
-
Human immunodeficiency virus
- HOPS:
-
Homotypic fusion and vacuole protein sorting
- KSHV:
-
Kaposi sarcoma-associated herpesvirus
- (m)TOR:
-
(Mechanistic/mammalian) target of rapamycin
- (MAP1)LC3:
-
(Microtubule-associated protein 1) light chain 3
- (m)TORC1:
-
(Mechanistic/mammalian) TOR complex 1
- PAS:
-
Pre-autophagosomal structure or phagophore assembly site
- PD:
-
Parkinson’s disease
- PI3P:
-
Phosphatidylinositol 3-phosphate
- SENDA:
-
Static encephalopathy of childhood with neurodegeneration in adulthood
- SNARE:
-
Soluble NSF Attachment Protein (SNAP) receptor
- ULK:
-
unc51-like kinase
- UVRAG:
-
Ultra violet radiation resistance associated gene
- VPS:
-
Vacuolar protein sorting
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Lippai, M., Szatmári, Z. Autophagy—from molecular mechanisms to clinical relevance. Cell Biol Toxicol 33, 145–168 (2017). https://doi.org/10.1007/s10565-016-9374-5
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DOI: https://doi.org/10.1007/s10565-016-9374-5