Autophagy regulation

Autophagy is a highly conserved catabolic process where cells degrade and recycle their own components, such as damaged organelles and misfolded proteins, through lysosomal pathways to maintain cellular homeostasis (NIH/NCBI, 2019). The term 'Autophagy regulation' refers to the complex signaling network—primarily governed by the Mechanistic Target of Rapamycin Complex 1 (mTORC1) and AMP-activated protein kinase (AMPK)—that controls the initiation, maturation, and fusion of autophagosomes (Nature Reviews Drug Discovery, 2017). Dysregulation of this process is implicated in numerous pathologies; for instance, impaired autophagy leads to the accumulation of toxic aggregates in neurodegenerative diseases, while in cancer, autophagy can paradoxically support tumor survival under metabolic stress (PubMed, 2021). Therapeutic strategies target various steps of this pathway using mTOR inhibitors like Sirolimus to induce autophagy or lysosomal inhibitors like Hydroxychloroquine to arrest it (Wikipedia, 2023). However, because 'Autophagy regulation' describes a broad biological mechanism rather than a single molecular entity, it is considered a pathway/process rather than a discrete therapeutic target (UniProt, 2023). Precise modulation remains a challenge due to the risk of off-target systemic effects and the context-dependent nature of autophagy's role in different tissues and disease stages.

Other names

Macroautophagy regulationAutophagic flux controlAutophagic pathwayCellular self-eating process

Drugs modulate autophagy by either inhibiting the master negative regulator mTORC1 to induce the pathway, activating AMPK to trigger initiation, or using lysosomotropic agents to block the fusion and degradation stages.