PI3P phosphatase activity is required for autophagosome maturation and autolysosome formation

Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology submitted time 2016-05-18

Wu, Yanwei Wu, Yanwei Cheng, Shiya Zou, Wei Wang, Xiaochen Zhao, Hongyu Zhang, Hong Yoshina, Sawako Mitani, Shohei Yoshina, Sawako Mitani, Shohei

Abstract： 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.

Peer Review Status:Awaiting Review

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