PI3P phosphatase activity is required for autophagosome maturation and autolysosome formation

• Published in: EMBO reports Vol. 15; no. 9; pp. 973 - 981
• Main Authors: Wu, Yanwei, Cheng, Shiya, Zhao, Hongyu, Zou, Wei, Yoshina, Sawako, Mitani, Shohei, Zhang, Hong, Wang, Xiaochen
• Format: Journal Article
• Language: English
• Published: London Blackwell Publishing Ltd 01.09.2014; Nature Publishing Group UK; Springer Nature B.V; BlackWell Publishing Ltd
• Subjects: Animals; autolysosome; Autophagy; Autophagy - genetics; Caenorhabditis elegans; Caenorhabditis elegans Proteins - metabolism; EMBO07; EMBO20; Enzymes; Kinases; Lysosomes - genetics; Lysosomes - metabolism; Molecular biology; MTM-3; Nematodes; Phagosomes - genetics; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Phosphatidylinositol Phosphates - metabolism; Phosphoric Monoester Hydrolases - metabolism; Protein Tyrosine Phosphatases, Non-Receptor - metabolism; PtdIns3P; Scientific Report; Scientific Reports; MTM‐3; autophagy; autolysosome; PtdIns3P; Caenorhabditis elegans
• ISSN: 1469-221X; 1469-3178; 1469-3178
• DOI: 10.15252/embr.201438618

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. Synopsis The PI3P phosphatase MTM‐3 is required for autophagosome maturation and autolysosome formation in C. elegans , highlighting the importance of reducing PI3P levels at the autophagosomal membrane during these late steps of autophagy. Caenorhabditis elegans myotubularin phosphatase MTM‐3 promotes autophagosome maturation into autolysosome. MTM‐3 is recruited by and catalyzes turnover of PtdIns3P on autophagosomes. Graphical Abstract The PI3P phosphatase MTM‐3 is required for autophagosome maturation and autolysosome formation in C. elegans , highlighting the importance of reducing PI3P levels at the autophagosomal membrane during these late steps of autophagy.