From the Guidelines
Autophagy is a complex cellular process involving the degradation and recycling of cellular components, such as damaged organelles and proteins, to maintain cellular homeostasis and adapt to stress conditions.
Key Steps of Autophagy
- Induction: triggered by cellular stressors, such as nutrient deprivation, oxidative stress, or damaged proteins/organelles, activating signaling pathways like MTOR and AMPK 1
- Nucleation: formation of a double-membraned phagophore, involving key complexes like ULK and phosphatidylinositol 3-kinase/PtdIns3K 1
- Expansion and elongation: phagophore expansion and elongation, forming a complete autophagosome, requiring the ATG12-ATG5-ATG16L1 complex 1
- Cargo recognition and sequestration: autophagosome recognizes and sequesters specific cargo, such as damaged organelles, protein aggregates, or invading pathogens, mediated by autophagy receptors 1
- Fusion with a lysosome: mature autophagosome fuses with a lysosome, forming an autolysosome, enabling degradation of sequestered cargo by lysosomal hydrolases 1
- Cargo degradation and recycling: cargo inside the autolysosome is degraded by lysosomal enzymes, and breakdown products are released into the cytoplasm for recycling and reuse by the cell 1
Types of Autophagy
- Macroautophagy: non-specific autophagic sequestration of cytoplasm into a double-membrane-delimited compartment, followed by degradation by the lysosomal system 1
- Chaperone-mediated autophagy (CMA): import and degradation of soluble cytosolic proteins by chaperone-dependent, direct translocation across the lysosomal membrane 1
- Selective autophagy: includes processes like xenophagy (degradation of microbes) and reticulophagy (degradation of the ER) 1
From the Research
Definition of Autophagy
- Autophagy is a highly conserved lysosomal degradation pathway active at basal levels in all cells 2, 3, 4, 5, 6
- It is a catabolic process by which cells recycle cytoplasmic components and superfluous or damaged organelles to preserve metabolic homeostasis under normal conditions and promote survival under stress 3
- Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome 4
- It is a lysosomal degradation process and protective housekeeping mechanism to eliminate damaged organelles, long-lived misfolded proteins and invading pathogens 5
- Autophagy is a highly conserved eukaryotic cellular recycling process that plays important roles in cell survival and maintenance 6
Role of Autophagy
- Autophagy has critical roles in development and cell differentiation, immune function, organismal health and lifespan 3
- It allows cells to adapt to stress and recycle building blocks and energy for cellular renovation and homeostasis 5
- Autophagy is essential for maintaining cell homeostasis, particularly in post-mitotic cells such as neurons, to get rid of damaged and/or old organelles and misfolded or aggregated proteins 2
- Dysfunctional autophagy contributes to the pathologies of many human diseases, including liver disease, cardiovascular, cerebrovascular diseases, neurodegenerative diseases, neoplastic diseases, cancers, and infectious diseases 2, 3, 6