Image-based genome-wide siRNA screen identifies selective autophagy factors

Anthony Orvedahl, Rhea Sumpter, Guanghua Xiao, Aylwin Ng, Zhongju Zou, Yi Tang, Masahiro Narimatsu, Christopher Gilpin, Qihua Sun, Michael Roth, Christian V. Forst, Jeffrey L. Wrana, Ying E. Zhang, Katherine Luby-Phelps, Ramnik J. Xavier, Yang Xie and Beth Levine ()
Additional contact information
Anthony Orvedahl: University of Texas Southwestern Medical Center
Rhea Sumpter: University of Texas Southwestern Medical Center
Guanghua Xiao: University of Texas Southwestern Medical Center
Aylwin Ng: Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School
Zhongju Zou: University of Texas Southwestern Medical Center
Yi Tang: Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Masahiro Narimatsu: Center for Systems Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Christopher Gilpin: University of Texas Southwestern Medical Center
Qihua Sun: University of Texas Southwestern Medical Center
Michael Roth: University of Texas Southwestern Medical Center
Christian V. Forst: University of Texas Southwestern Medical Center
Jeffrey L. Wrana: Center for Systems Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Ying E. Zhang: Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Katherine Luby-Phelps: University of Texas Southwestern Medical Center
Ramnik J. Xavier: Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School
Yang Xie: University of Texas Southwestern Medical Center
Beth Levine: University of Texas Southwestern Medical Center

Nature, 2011, vol. 480, issue 7375, 113-117

Abstract: Abstract Selective autophagy involves the recognition and targeting of specific cargo, such as damaged organelles, misfolded proteins, or invading pathogens for lysosomal destruction1,2,3,4. Yeast genetic screens have identified proteins required for different forms of selective autophagy, including cytoplasm-to-vacuole targeting, pexophagy and mitophagy, and mammalian genetic screens have identified proteins required for autophagy regulation5. However, there have been no systematic approaches to identify molecular determinants of selective autophagy in mammalian cells. Here, to identify mammalian genes required for selective autophagy, we performed a high-content, image-based, genome-wide small interfering RNA screen to detect genes required for the colocalization of Sindbis virus capsid protein with autophagolysosomes. We identified 141 candidate genes required for viral autophagy, which were enriched for cellular pathways related to messenger RNA processing, interferon signalling, vesicle trafficking, cytoskeletal motor function and metabolism. Ninety-six of these genes were also required for Parkin-mediated mitophagy, indicating that common molecular determinants may be involved in autophagic targeting of viral nucleocapsids and autophagic targeting of damaged mitochondria. Murine embryonic fibroblasts lacking one of these gene products, the C2-domain containing protein, SMURF1, are deficient in the autophagosomal targeting of Sindbis and herpes simplex viruses and in the clearance of damaged mitochondria. Moreover, SMURF1-deficient mice accumulate damaged mitochondria in the heart, brain and liver. Thus, our study identifies candidate determinants of selective autophagy, and defines SMURF1 as a newly recognized mediator of both viral autophagy and mitophagy.

Date: 2011
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature10546 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:480:y:2011:i:7375:d:10.1038_nature10546

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature10546

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().