A diacylglycerol-dependent signaling pathway contributes to regulation of antibacterial autophagy

Shahab Shahnazari, Wei Lien Yen, Cheryl L. Birmingham, Jessica Shiu, Anton Namolovan, Yiyu T. Zheng, Keiko Nakayama, Daniel J. Klionsky, John H. Brumell

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

Autophagy mediates the degradation of cytoplasmic contents in the lysosome and plays a significant role in immunity. Lipid second messengers have previously been implicated in the regulation of autophagy. Here, we demonstrate a signaling role for diacylglycerol (DAG) in antibacterial autophagy. DAG production was necessary for efficient autophagy of Salmonella, and its localization to bacteria-containing phagosomes preceded autophagy. The actions of phospholipase D and phosphatidic acid phosphatase were required for DAG generation and autophagy. Furthermore, the DAG-responsive δ isoform of protein kinase C was required, as were its downstream targets JNK and NADPH oxidase. Previous studies have revealed a role for the ubiquitin-binding adaptor molecules p62 and NDP52 in autophagy of S. Typhimurium. We observed bacteria-containing autophagosomes colocalizing individually with either DAG or ubiquitinated proteins, indicating that both signals can act independently to promote antibacterial autophagy. These findings reveal an important role for DAG-mediated PKC function in mammalian antibacterial autophagy.

Original languageEnglish
Pages (from-to)137-146
Number of pages10
JournalCell Host and Microbe
Volume8
Issue number2
DOIs
Publication statusPublished - 2010 Aug 19

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

Fingerprint Dive into the research topics of 'A diacylglycerol-dependent signaling pathway contributes to regulation of antibacterial autophagy'. Together they form a unique fingerprint.

  • Cite this

    Shahnazari, S., Yen, W. L., Birmingham, C. L., Shiu, J., Namolovan, A., Zheng, Y. T., Nakayama, K., Klionsky, D. J., & Brumell, J. H. (2010). A diacylglycerol-dependent signaling pathway contributes to regulation of antibacterial autophagy. Cell Host and Microbe, 8(2), 137-146. https://doi.org/10.1016/j.chom.2010.07.002