Macroautophagy pathway components

Macroautophagy is a fundamental, evolutionarily conserved cellular process responsible for the degradation and recycling of cytoplasmic components, including misfolded proteins and damaged organelles (NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424777/). This pathway involves the formation of double-membrane vesicles called autophagosomes that engulf cellular cargo and subsequently fuse with lysosomes for enzymatic breakdown (ResearchGate, https://www.researchgate.net/publication/384814411_Autophagy_Mechanism_and_Clinical_Potential). The process is regulated by a complex network of proteins, including the ULK1 initiation complex, the VPS34 nucleation complex, and various autophagy-related (ATG) proteins (Frontiers, https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1534211/full). Macroautophagy plays a critical role in maintaining cellular homeostasis and responding to nutrient stress, and its dysfunction is linked to a wide range of pathologies such as neurodegenerative diseases, cancer, and infections (NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424777/). In therapeutic contexts, the pathway is targeted either to enhance its protective recycling function (e.g., using mTOR inhibitors like rapamycin) or to inhibit its survival-promoting effects in established tumors (e.g., using lysosomal inhibitors like hydroxychloroquine) (MDPI, https://www.mdpi.com/1422-0067/25/20/10965).

Other names

Autophagy pathwayMacroautophagy machineryATG systemAutophagy-lysosomal pathway

mTORC1 inhibition (autophagy induction), Lysosomal acidification inhibition (autophagy inhibition), ULK1 kinase inhibition, VPS34 kinase inhibition, AMPK activation (autophagy induction), and v-ATPase inhibition (autophagy inhibition)