Analysis of the Molecular Mechanism of Autophagosome Formation in Saccharomyces Cerevisiae.

Autophagy;Molecular;Cellular and Developmental Biology;Science;Molecular, Cellular, and Developmental Biology

Yen, Wei-LienWeisman, Lois ;

University of Michigan

关键词: Autophagy;    Molecular;    Cellular and Developmental Biology;    Science;    Molecular, Cellular, and Developmental Biology;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/64619/wlyen_2.pdf?sequence=2&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Autophagy is an evolutionarily conserved catabolic pathway, which is involved in the degradation of long-lived proteins, organelles, and a large portion of the cytoplasm in response to internal and external stresses, such as nutrient starvation. In addition, autophagy is involved in development, and plays a cytoprotective role by removing protein aggregates, and damaged or superfluous organelles. Defects in autophagy are associated with various diseases, such as cancer, gastrointestinal disorders and neurodegeneration.During autophagy, the cargos that are targeted for degradation are sequestered into double-membrane vesicles. However, the mechanisms of vesicle formation and completion as well as the membrane source(s) remain unclear. One of the autophagy-related (Atg) transmembrane proteins, Atg9, is a candidate to mediate the delivery of lipid from the membrane source(s) to the forming autophagosome. This protein displays a unique subcellular localization pattern, residing and cycling between the phagophore assembly site (PAS, the site where the autophagosome is generated), mitochondria, and other peripheral sites. Atg9 forms a functional complex with Atg23 and Atg27. These proteins colocalize, interact with one another in vivo, and depend upon one another for their movements. One of the Atg9 complex components, Atg27, is a type I transmembrane protein. It localizes to the PAS, Golgi complex, and mitochondria. It regulates Atg9 cycling from the mitochondria to the PAS. The proper function of Atg27 is required for efficient autophagy. The correct localization and transit patterns of Atg27 and Atg9 are dependent on each other suggesting that these two proteins may function in concert, bringing membrane to the PAS.During the double-membrane vesicle formation process, transient vesicles derived from the membrane source(s) have to fuse with the expanding phagophore at the PAS. However, little is known about the components involved in this fusion event. The conserved oligomeric Golgi (COG) complex, is found to localize in part at the PAS. The interactions between COG complex components and Atg proteins suggest the direct involvement of this tethering complex in autophagy. A role for the COG complex also provides a better understanding of the membrane tethering and fusion events that occur during double-membrane vesicle formation.