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细胞自噬的分子机制 Ⅲ型磷脂酰肌醇三磷酸激酶(ClassⅢPI3K) PI3 kinase type III, which includes Atg6 in its complex, promotes the nucleation of autophagic vesicles. * 自噬的生理和病理意义 广泛存在于正常的生理过程中:如清除细胞废物、结构重建、生长分化等 细胞对不良环境的一种防御机制:如对抗营养缺乏、电离辐射 参与多种疾病的病理过程:无论是自噬过度还是自噬不足都可能导致疾病发生 * * Physiological Functions of Autophagy Autophagy Defends against Metabolic Stress Autophagy Works as a Cellular Housekeeper Autophagy May Be a Guardian of the Genome Autophagy in Life and Death Decisions of the Cell * 1. Autophagy Defends against Metabolic Stress Autophagy is activated as an adaptive catabolic process in response to different forms of metabolic stress: nutrient deprivation growth factor depletion hypoxia * * * 2. Autophagy Works as a Cellular Housekeeper Housekeeping functions performed by autophagy includes: the elimination of defective proteins and organelles the prevention of abnormal protein aggregate accumulation the removal of intracellular pathogens Critical for autophagy-mediated protection against aging, cancer, neurodegenerative diseases, and infection * 3. Autophagy May Be a Guardian of the Genome Autophagy-defective cells: genomic instability. Related to: failure to control the damage of checkpoint or repair proteins, deregulated turnover of centrosomes, insuficient energy for proper DNA replication and repair excessive generation of reactive oxygen species due to ineficient removal of damaged mitochondria The precise mechanisms are unclear * 4. Autophagy in Life and Death Decisions of the Cell Autophagy can independently inluence life and death decisions of the cell (by being cytoprotective or selfdestructive), it is also intricately linked to apoptotic death pathways Factors that may control the cellular “decision” between the autophagy and apoptosis include: potentially variable thresholds for each process molecular links that coordinately regulate apoptosis and autophagy mutual inhibition or activation of each pathway by the other
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