regulation of autophagy

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of autophagy. Autophagy is the process in which cells digest parts of their own cytoplasm. [GOC:dph, GOC:tb]

Autophagy is a highly regulated cellular process involving the formation of double-membrane vesicles called autophagosomes, which engulf cytoplasmic components, including organelles, protein aggregates, and pathogens. These autophagosomes then fuse with lysosomes, where the enclosed material is degraded. Autophagy plays a crucial role in maintaining cellular homeostasis by removing damaged or unnecessary cellular components, recycling cellular building blocks, and responding to various stresses. It is essential for cellular survival, development, and immunity.

Autophagy is tightly regulated by a complex network of signaling pathways, including the mTOR, AMPK, and MAPK pathways. These pathways integrate various cellular signals, such as nutrient availability, growth factor signaling, and stress, to fine-tune autophagy activity.

**Initiation and Formation of Autophagosomes:**
1. **Induction:** Autophagy initiation is triggered by signaling pathways, such as the mTOR pathway. When nutrient levels are low, the mTOR pathway is inhibited, leading to the activation of the autophagy-related (ATG) proteins.
2. **Nucleation:** The ATG proteins, including ATG1/ULK1 complex and ATG9, assemble at specific sites in the cytoplasm to initiate the formation of the autophagosome membrane.
3. **Elongation:** The autophagosome membrane elongates through the recruitment of additional ATG proteins, including ATG5-ATG12-ATG16L1 complex and LC3/GABARAP proteins. LC3/GABARAP proteins are essential for the elongation and closure of the autophagosome membrane.
4. **Closure:** The autophagosome membrane eventually encloses a portion of the cytoplasm, forming a closed autophagosome.

**Fusion with Lysosomes:**
1. **Targeting:** After formation, the autophagosome travels to the lysosome, facilitated by proteins like LAMP2.
2. **Fusion:** The autophagosome membrane fuses with the lysosomal membrane, releasing its enclosed cargo into the lysosomal lumen.

**Degradation and Recycling:**
1. **Hydrolysis:** Lysosomal hydrolytic enzymes degrade the engulfed material into their basic building blocks, including amino acids, fatty acids, and nucleotides.
2. **Recycling:** These breakdown products are released back into the cytoplasm, providing nutrients and building blocks for cellular functions.

**Regulation by Signaling Pathways:**

* **mTOR Pathway:** The mTOR pathway is a major negative regulator of autophagy. When nutrients are abundant, mTOR is activated, suppressing autophagy. Conversely, nutrient deprivation or stress inhibits mTOR, leading to autophagy activation.
* **AMPK Pathway:** The AMPK pathway is a positive regulator of autophagy. AMPK is activated by cellular energy depletion, promoting autophagy.
* **MAPK Pathway:** The MAPK pathway can both activate and inhibit autophagy depending on the specific MAPK involved and the cellular context.

Autophagy plays critical roles in various cellular processes, including:

* **Cell survival:** By removing damaged organelles and protein aggregates, autophagy maintains cellular integrity and promotes survival during stress conditions.
* **Development:** Autophagy is essential for normal embryonic development and organogenesis.
* **Immunity:** Autophagy participates in the elimination of intracellular pathogens and the presentation of antigens to immune cells.
* **Disease:** Dysregulation of autophagy is implicated in a variety of diseases, including cancer, neurodegenerative disorders, and infectious diseases.'
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Compounds (608)