Data from: HS1BP3 negatively regulates autophagy by modulation of phosphatidic acid levels

Holland, Petter, University of Oslo

Knævelsrud, Helene, University of Oslo

Søreng, Kristiane, University of Oslo

Mathai, Benan John, University of Oslo

Lystad, Alf Håkon, University of Oslo

Pankiv, Serhiy, University of Oslo

Bjørndal, Gunnveig T., University of Oslo

Schultz, Sebastian W., University of Oslo

Lobert, Viola H., University of Oslo

Chan, Robin B., Columbia University

Zhou, Bowen, Columbia University

Liestøl, Knut, University of Oslo

Carlsson, Sven R., Umeå, Sweden

Melia, Thomas J., Yale School of Medicine

Di Paolo, Gilbert, Columbia University

Simonsen, Anne, University of Oslo

Published Oct 27, 2017 on Dryad. https://doi.org/10.5061/dryad.gq3fk

Cite this dataset

Holland, Petter et al. (2017). Data from: HS1BP3 negatively regulates autophagy by modulation of phosphatidic acid levels [Dataset]. Dryad. https://doi.org/10.5061/dryad.gq3fk

Abstract

A fundamental question is how autophagosome formation is regulated. Here we show that the PX domain protein HS1BP3 is a negative regulator of autophagosome formation. HS1BP3 depletion increased the formation of LC3-positive autophagosomes and degradation of cargo both in human cell culture and in zebrafish. HS1BP3 is localized to ATG16L1- and ATG9-positive autophagosome precursors and we show that HS1BP3 binds phosphatidic acid (PA) through its PX domain. Furthermore, we find the total PA content of cells to be significantly upregulated in the absence of HS1BP3, as a result of increased activity of the PA-producing enzyme phospholipase D (PLD) and increased localization of PLD1 to ATG16L1-positive membranes. We propose that HS1BP3 regulates autophagy by modulating the PA content of the ATG16L1-positive autophagosome precursor membranes through PLD1 activity and localization. Our findings provide key insights into how autophagosome formation is regulated by a novel negative-feedback mechanism on membrane lipids.

Usage notes

Compiled Lipidomics Data_NCOMMS-16-13893-A

Raw data of MS lipidomics datasets used in Fig. 5a and Supplementary Fig. 4c. Data are from HEK cells treated with non-targeting (Control) or HS1BP3 siRNA starved for 2 hrs (mean +/- SEM., n = 6). See the Methods section for a full description of the Methods used.