2014分子病理学.ppt

细胞自噬的类型 Mitophagy : mitochondria Pexophagy: peroxisomes, Reticulophagy: endoplasmic reticulum Organelle?selective modes selective autophagy Physiological and Pathphysiological Roles of Autophagy 我 们 的 团 队 谢 谢 * 自噬的生理学与病理生理学作用 Physiological and Pathphysiological Roles of Autophagy Protein degradation system Ubiquitin-proteasome Autophagy–lysosome ≈1% ≈ 99% 5 hours 5 hours 1980 1962 2004 ? Nobel Prize Discovery Half-life Percentage E1(泛素活化酶) E2(泛素结合酶) E3(泛素-蛋白连接酶) 比利时科学家德·迪夫 衰老的线粒体 衰老的过氧化物酶体 Function of autophagy ? Housekeeping mechanism involved in cytoplasmic homeostasis B. Involved in certain tissue-specific functions Cell Death Immune Response Development and Aging C. Autophagy in Disease Cancer Neurodegenerative diseases Parkinson, Huntington, Alzheimer Muscular diseases Human cardian Skeletal myopathic Danon disease autophagy (‘self-eating’) Apoptosis (‘self-killing’) Not good OR bad but good AND bad Autophagy 巨型自噬 (macroautophagy) 微型自噬 (microautophagy) 分子伴侣介导的自噬 (chaperon-mediated autophagy) 细胞自噬的类型 细胞自噬的类型 细胞自噬的机制 The machinery of autophagy Molecular regulation mechanism of autophagy PI3K-Akt-mTOR LKB1-AMPK-mTOR Beclin1-Bcl-2 p53 Other mechanisms Molecules and their functions in autophagy Identification of Atg genes and their functions. mTOR regulation of autophagy Crosstalk between ER stress, apoptosis and autophagy pathways