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AUTOPHAGY Parvinderdeep Singh Kahlon PCDU Seminar WS 2015/2016 1 https://goo.gl/gz5oJA CONTENT Introduction Role of Autophagy Types of Autophagic Processes Summary http://www.contentfirst.com/images/information_Istock.jpg 2 INTRODUCTION [1] Autophagy, the process of cellular self-eating, is an important protein degradation pathway, particularly during starvation or stress. It is as a bulk process which degrade long-lived proteins and organelles such as the endoplasmic reticulum, mitochondria, peroxisomes, the nucleus and ribosomes [2,3] In contrast to the ubiquitin–proteasome system (UPS), which targets individual short-lived proteins [1] http://pilotfire.com/wp-content/uploads/autophagy.png [2] Mizushima, N. & Klionsky, D. J. 2007. Protein turnover via autophagy: implications for metabolism. Annu. Rev. Nutr. 27, 19–40. [3] Stolz, A., Ernst, A. & Dikic, I. 2014. Cargo recognition and trafficking in selective autophagy. Nat. Cell Biol. 16, 495–501 . 3 ROLE OF AUTOPHAGY Autophagic degradation promotes the recycling and salvage of cellular nutrients, thereby enabling cell survival during starvation. Along with the UPS, helps in protein homeostasis and quality control. It also plays a key part in mobilizing diverse cellular energy and nutrient stores, including carbohydrates, lipids and minerals. Kaur J and Debnath J. 2015. Autophagy at the crossroads of catabolism and anabolism. Nature Reviews : 16;461 472 4 TYPES Autophagy refers to a collection of tightly regulated catabolic processes, all of which deliver cytoplasmic components to the lysosome for degradation In animals and yeasts, autophagy is often divided into three main types: Chaperone-mediated autophagy, Microautophagy, Macroautophagy. 5 http://www.nature.com/nrgastro/journal/v11/n3/images/nrgastro .2013.211-f1.jpg DETAILED PROCESS Kaur J and Debnath J. 2015. Autophagy at the crossroads of catabolism and anabolism. Nature Reviews : 16;461 472 6 CHAPERONE-MEDIATED AUTOPHAGY Target protein binds to a chaperone protein. The target protein then is transported to a lysosome, becomes unfolded and is taken up by direct translocation across the lysosomal membrane. It occurs only in mammalian cells but it cannot be excluded that a similar mechanism occurs in plants. Doorn WG and Papini A. 2013. Ultrastructure of autophagy in plant cells .Autophagy 9:12, 1–15 7 MICROAUTOPHAGY It is the process of uptake of cellular constituents by the lysosomal/vacuolar membrane. The membrane surrounds a portion of the cytoplasm, merges with itself, and then undergoes scission. This results in a portion of the cytoplasm, surrounded by a piece of lysosomal/vacuolar membrane, inside the lysosome/ vacuole. May AI, Devenish RJ, Prescott M. 2012 The many faces of mitochondrial autophagy: Making sense of contrasting observations in recent research. Int J Cell Biol,1-18. 8 DIAGRAMMATIC OVERVIEW (A) Invagination (A1) or protrusion (A2) of the vacuolar membrane, resulting in the uptake of a portion of the cytoplasm. (B) Invagination membrane-bound vesicle in the cytoplasm is taken up by the vacuole Doorn WG and Papini A. 2013. Ultrastructure of autophagy in plant cells .Autophagy 9:12, 1–15 9 EXAMPLE OF MICROAUTOPHAGY (A and B) Invaginations into the vacuole. (C) Rubber particles in cytoplasm and vacuole D) Senescing petals of carnation flowers Doorn WG and Papini A. 2013. Ultrastructure of autophagy in plant cells .Autophagy 9:12, 1–15 10 MACROAUTOPHAGY Macroautophagy is performed in the cytoplasm, whereby a portion of the cytoplasm is sequestered inside a doublemembrane-bound organelle. Hydrolases take place, away from the vacuole. The cytoplasmic material is broken down inside this structure by small tubules formation or membranes formation at the ER Bassham DC, Laporte M, Marty F, Moriyasu Y, Ohsumi Y, Olsen LJ, Yoshimoto K. 2006. Autophagy in development and stress responses of plants. Autophagy 2:2-11. 11 DIAGRAMMATIC OVERVIEW (A) small tubules are formed in the cytoplasm (B) membranes with an ER-like structure are formed at theER Doorn WG and Papini A. 2013. Ultrastructure of autophagy in plant cells .Autophagy 9:12, 1–15 12 EXAMPLE OF MACROAUTOPHAGY (A) Formation of a cagelike structure (B–D) Various stages of autophagosome/ autolysosome formation 13 Doorn WG and Papini A. 2013. Ultrastructure of autophagy in plant cells .Autophagy 9:12, 1–15 PROGRAMMED CELL DEATH (PCD) during normal development and after abiotic stress (developmental PCD) 2. after invasion by a pathogen (pathogen-related PCD). Massive autophagy (called mega-autophagy) is typical for the final phase of developmental PCD. 1. • • • • rupture of the vacuolar membrane release of large amounts of hydrolases into the cytoplasm. degrade the cytoplasm This results in cell death Doorn WG and Papini A. 2013. Ultrastructure of autophagy in plant cells .Autophagy 9:12, 1–15 14 PCD AT TIME OF BACTERIAL INFECTION 15 In plants, (AtMC1) positively regulates HR cell death mediated by NB-LRR recognition of the invading pathogen at the site of infection. LSD1 negatively regulates cell death propagation in cells surrounding the infection site presumably by binding to AtMC1 and holding it inactive in the cytoplasm.. Coll NS et al., 2011. Programmed cell death in the plant immune system. Cell Death and Differentiation18, 1247–1256. INTERNAL DEGENERATION OF CHLOROPLASTS Membrane bound vesicles with degradation products are formed inside the organelle. These vesicles move into the cytoplasm and are subsequently taken up by the vacuole where they become degraded. Doorn WG and Papini A. 2013. Ultrastructure of autophagy in plant cells .Autophagy 9:12, 1–15 16 SCHEMATIC OVERVIEW Proposed model of the degradation of Rubisco and possibly other stromal proteins by ATGdependent autophagy via RCBs Ishida H et al., 2008. Mobilization of Rubisco and Stroma-Localized Fluorescent Proteins of Chloroplasts to the Vacuole by an ATG Gene-Dependent Autophagic Process.. Plant Physiology, 148: 142-155 17 SUMMARY Autophagy, the process of cellular selfeating recycling and salvage of cellular nutrients, protein homeostasis, mobilizing diverse cellular energy and nutrient stores In yeast and mammals majorly divided into three main types, plants have addition types 18 •Presently little is known about the ultrastructure of autophagy in plants •Extensive research is yet needed to know the unknown Thank You 19