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1. chinaXiv:201605.01803 [pdf]

PI3P phosphatase activity is required for autophagosome maturation and autolysosome formation

Wu, Yanwei; Wu, Yanwei; Cheng, Shiya; Zou, Wei; Wang, Xiaochen; Zhao, Hongyu; Zhang, Hong; Yoshina, Sawako; Mitani, Shohei; Yoshina, Sawako; Mitani, Shohei
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology

Autophagosome formation is promoted by the PI3 kinase complex and negatively regulated by myotubularin phosphatases, indicating that regulation of local phosphatidylinositol 3-phosphate (PtdIns3P) levels is important for this early phase of autophagy. Here, we show that the Caenorhabditis elegans myotubularin phosphatase MTM-3 catalyzes PtdIns3P turnover late in autophagy. MTM-3 acts downstream of the ATG-2/EPG-6 complex and upstream of EPG-5 to promote autophagosome maturation into autolysosomes. MTM-3 is recruited to autophagosomes by PtdIns3P, and loss of MTM-3 causes increased autophagic association of ATG-18 in a PtdIns3P-dependent manner. Our data reveal critical roles of PtdIns3P turnover in autophagosome maturation and/or autolysosome formation.

submitted time 2016-05-18 Hits11040Downloads1480 Comment 0

2. chinaXiv:201605.01461 [pdf]

Guidelines for monitoring autophagy in Caenorhabditis elegans

Zhang, Hong; Guo, Bin; Lin, Long; Lu, Qun; Wu, Fan; Chang, Jessica T.; Hansen, Malene; Kumsta, Caroline; Lapierre, Louis R.; Jia, Kailiang; Kovacs, Attila L.; Legouis, Renaud; Melendez, Alicia; Melendez, Alicia; O'Rourke, Eyleen J.; Sato, Ken; Sato, Miyuki; Wang, Xiaochen
Subjects: Biology >> Biophysics >> Cell Biology

The cellular recycling process of autophagy has been extensively characterized with standard assays in yeast and mammalian cell lines. In multicellular organisms, numerous external and internal factors differentially affect autophagy activity in specific cell types throughout the stages of organismal ontogeny, adding complexity to the analysis of autophagy in these metazoans. Here we summarize currently available assays for monitoring the autophagic process in the nematode C. elegans. A combination of measuring levels of the lipidated Atg8 ortholog LGG-1, degradation of well-characterized autophagic substrates such as germline P granule components and the SQSTM1/p62 ortholog SQST-1, expression of autophagic genes and electron microscopy analysis of autophagic structures are presently the most informative, yet steady-state, approaches available to assess autophagy levels in C. elegans. We also review how altered autophagy activity affects a variety of biological processes in C. elegans such as L1 survival under starvation conditions, dauer formation, aging, and cell death, as well as neuronal cell specification. Taken together, C. elegans is emerging as a powerful model organism to monitor autophagy while evaluating important physiological roles for autophagy in key developmental events as well as during adulthood.

submitted time 2016-05-12 Hits1966Downloads1214 Comment 0

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