浙江大学医学院：自噬与免疫（PPT讲稿）Autophagy and Immunity

Autophagy and immunity Jianzhong Chen Institute of Immunology Zhejiang University School of Medicine Nov1,2013

Autophagy and Immunity Jianzhong Chen Institute of Immunology Zhejiang University School of Medicine Nov 1, 2013

Autophagy Phagy eating/lysosomal degradation Autophagy self-eating Mechanism of breakdown of cytoplasm within the ysosome Autophagy: a basic cellular process in eukaryotes 细胞在外界环境因素的影响下,对其内部受损的细胞器、错 误折叠的蛋白质及侵入其内的病原体进行降解的过程

Phagy = eating/lysosomal degradation Autophagy = self-eating Mechanism of breakdown of cytoplasm within the lysosome Autophagy: a basic cellular process in eukaryotes 细胞在外界环境因素的影响下，对其内部受损的细胞器、错 误折叠的蛋白质及侵入其内的病原体进行降解的过程。 Autophagy

Autophagy: a basic cellular process in eukaryotes Phagy eating/lysosomal degradation Autophagy self-eating Mechanism of breakdown of cytoplasm within the lysosome Plasma membrane Endocytosis Amorism heterophagy)\ Endosome Membrane proteIn Atcp Autolysosome Cytoplasm C Permease Acid hydrolase Klionsky, Nature Reviews Molecular cell Biology, Ly≥ scmc 2007,p.931

发现 Lysosome osone Golgi Christian de Duve1974

发现

发现 比利时科学家 Christian de duve在上世纪50 年代通过电镜观察到自噬体结构,并且在 1963年溶酶体国际会议上首先提出了“自噬 ”这种说法。因此 Christian de duve被公认 为自噬研究的鼻祖。 Christian de duve也因 发现溶酶体,于1974年获得诺贝尔奖。 ■“细胞自噬研究”是2013年诺贝尔生理学或 医学奖预测的热门领域

发现 ◼ 比利时科学家Christian de Duve在上世纪50 年代通过电镜观察到自噬体结构，并且在 1963 年溶酶体国际会议上首先提出了“自噬 ”这种说法。因此Christian de Duve被公认 为自噬研究的鼻祖。Christian de Duve 也因 发现溶酶体，于1974年获得诺贝尔奖。 ◼ “细胞自噬研究”是2013年诺贝尔生理学或 医学奖预测的热门领域

Autophagy: target Autophagic targets range in size and complexity n Individual long-lived macromolecules 口 Whole organelles a Microbial invaders

Autophagy: target ◼ Autophagic targets range in size and complexity  Individual long-lived macromolecules  Whole organelles  Microbial invaders

Autophagy: purposes (a quality control of disused or defunct organelles such as irreversibly depolarized or leaky mitochondria (b) removal of toxic macromolecular aggregates too large for handling by smaller capacity or single-molecule- handling proteolytic systems of the cell (e.g proteasome)

Autophagy: purposes ◼ (a) quality control of disused or defunct organelles such as irreversibly depolarized or leaky mitochondria; ◼ (b) removal of toxic macromolecular aggregates too large for handling by smaller capacity or single-molecule-handling proteolytic systems of the cell (e.g. proteasome);

Autophagy: purposes (c digestion of bulk cytoplasm expressly to replenish amino acids and energy during starvation or growth factor withdrawal (d) acting on or in concert with the molecular machineries and organelles at the interface between cell survival and cell death (e controlling and acting as an effector or a regulator of innate and adaptive immunity and Inflammation

Autophagy: purposes ◼ (c) digestion of bulk cytoplasm expressly to replenish amino acids and energy during starvation or growth factor withdrawal; ◼ (d) acting on or in concert with the molecular machineries and organelles at the interface between cell survival and cell death ◼ (e) controlling and acting as an effector or a regulator of innate and adaptive immunity and inflammation

Autophagy: Function The principal role of autophagy this ubiquitous eukaryotic homeostatic mechanism is to ensure cell survival under adverse conditions nutrient absence growth factor withdrawal accumulation of toxic protein aggregates Faulty organelles(e.g leaky mitochondria) infection by intracellular

Autophagy: Function ◼ The principal role of Autophagy this ubiquitous eukaryotic homeostatic mechanism is to ensure cell survival under adverse conditions ◼ nutrient absence, ◼ growth factor withdrawal ◼ accumulation of toxic protein aggregates ◼ Faulty organelles (e.g., leaky mitochondria) ◼ infection by intracellular

Autophagy Regulation Highly conserved and regulated process that maintains cellular homeostasis and protects cells against starvation and microbe invasion Birth wth Factor ental Interruption) riation Decreased Black in Extracellular Nutrients Nutrient Uptake creased intracellular Nutrients Mitochondria Nutrent Sensors TCAcvcle s Soning Events Protein Synthesis Falty Acids Autophagy Amino Acids Pre- Autophagosome Degradation of Structure cytoplasma Isolation Components Membrane Autophagosome Autolysosome Figure 1. Mammalian Autophagy in Cellular Defense against Two Forms of Nutrient Stress: Birth and Growth Factor Deprivation

Autophagy Regulation ◼ Highly conserved and regulated process that maintains cellular homeostasis and protects cells against starvation and microbe invasion