Autophagy signaling pathway

The autophagy signaling pathway is a fundamental, evolutionarily conserved process responsible for the degradation and recycling of cytoplasmic components, including damaged organelles and misfolded proteins, via the lysosomal machinery (StatPearls, 2023). It is primarily regulated by nutrient-sensing complexes, most notably the mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), which integrate signals from growth factors and energy status (Nature Reviews Molecular Cell Biology, 2018). In physiological conditions, autophagy maintains cellular homeostasis and provides essential nutrients during periods of starvation. However, its dysregulation is a hallmark of various diseases; for instance, impaired autophagy leads to the accumulation of toxic protein aggregates in neurodegenerative disorders like Alzheimer's, while in cancer, it can act as a double-edged sword by either suppressing early tumorigenesis or promoting the survival of established tumor cells (PubMed, 2021). Therapeutic strategies targeting this pathway include mTOR inhibitors like rapamycin to induce autophagy and lysosomotropic agents like chloroquine to inhibit it, though these approaches face challenges due to the pathway's complex, context-dependent roles in different tissues (PubChem, 2024).

Other names

MacroautophagyAutophagic fluxCellular self-eatingLysosomal degradation pathway

Pharmacological modulation of the autophagy signaling pathway involves the induction of autophagic flux through the inhibition of the mechanistic target of rapamycin (mTOR) or the activation of AMP-activated protein kinase (AMPK), as well as the inhibition of the pathway via the blockade of lysosomal acidification or the inhibition of class III phosphoinositide 3-kinase (PI3K) activity (StatPearls, 2023; PubChem, 2024).