Autophagie

Autophagie, also known as autophagy, is a cellular degradation process that enables the selective or bulk turnover of cytoplasmic constituents by delivering them to lysosomes for breakdown and recycling. It exists in three major forms: macroautophagie (macroautophagy), microautophagie (microautophagy) and chaperone-mediated autophagie (CMA). Macroautophagie is the best studied and typically forms autophagosomes that engulf cytoplasmic material before fusing with lysosomes. Microautophagie involves direct invagination of the lysosomal membrane, while CMA uses chaperone proteins to deliver specific soluble proteins to lysosomes.

Process overview: In macroautophagie initiation is regulated by nutrient and energy signals, notably the mTOR pathway, which restrains the ULK1 complex. Upon activation, a phagophore forms and expands, recruiting ATG proteins and the LC3 conjugation systems to generate autophagosomes. The mature autophagosome fuses with lysosomes to form an autolysosome, where cargo is degraded by lysosomal enzymes and the resulting macromolecules are recycled for new biosynthesis or energy.

Selective autophagie uses cargo receptors such as p62/SQSTM1 to bind specific targets like mitochondria (Mitophagie), peroxisomes (Pexophagie) or aggregated proteins (Aggrephagie). In contrast, bulk autophagie can non-selectively degrade cytoplasm during starving conditions.

Biological roles and clinical relevance: Autophagie maintains cellular homeostasis, clears damaged organelles, and defends against intracellular pathogens. It influences development, immune responses and aging. Dysregulation is linked to diseases including cancer, neurodegenerative disorders and metabolic syndromes. Because Autophagie can promote cell survival or contribute to cell death depending on context, therapeutic strategies aim to modulate autophagy carefully.

Measurement and regulation: Autophagie is regulated by nutrient sensing and energy status, with mTOR as a central brake. ATG genes and LC3/GABARAP family proteins are used as markers in research; p62/SQSTM1 accumulates when autophagie is impaired. Assessing autophagie flux, not only static markers, is important for understanding activity.