Abstract

Autophagy, a conserved lysosome-dependent degradation pathway, plays a fundamental role in maintaining cellular homeostasis by removing dysfunctional components and recycling essential cellular materials. Through this process, cells adapt to metabolic stress, maintain organelle integrity, and prevent the toxic accumulation of misfolded proteins and damaged organelles. Over recent years, the understanding of autophagy has evolved considerably, revealing its complex roles in physiology and disease. This review investigates the molecular regulation and mechanistic diversity of the three principal forms of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Each of these pathways plays distinct but complementary roles in cellular quality control, survival, and adaptation.
Key molecular regulators of autophagy, including mechanistic target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), unc-51-like kinase 1 (ULK1), and autophagy-related (ATG) proteins, orchestrate the induction, progression, and completion of the autophagic process. Their coordinated actions determine autophagic flux, which is highly responsive to cellular nutrient status and stress signals. Autophagy has been implicated in the pathogenesis of several major diseases. In cancer, it exhibits a paradoxical role: acting as a tumor-suppressive mechanism during early tumorigenesis while promoting cell survival and resistance to therapy in advanced cancers. In neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s disease, defective autophagy impairs clearance of toxic protein aggregates, exacerbating neuronal dysfunction, whereas therapeutic enhancement of autophagy holds neuroprotective potential. Additionally, autophagy is now recognized as a crucial regulator of immune responses, influencing inflammation, pathogen clearance, and antigen presentation.
Furthermore, the progressive decline of autophagic activity with age contributes to the accumulation of cellular damage and the onset of age-related diseases. A deeper understanding of the molecular networks controlling autophagy and its tissue-specific functions may provide innovative therapeutic strategies for cancer, neurodegeneration, immune-related disorders, and healthy aging.

Key words: Autographic; Cellular homeostasis; Immune response; Neurodegeneration; Therapeutic targets.