Next Article in Journal
Sex-Gender Variable: Methodological Recommendations for Increasing Scientific Value of Clinical Studies
Next Article in Special Issue
Autophagy in Synucleinopathy: The Overwhelmed and Defective Machinery
Previous Article in Journal
pHluorin-BACE1-mCherry Acts as a Reporter for the Intracellular Distribution of Active BACE1 In Vitro and In Vivo
Open AccessArticle

ER-Targeted Beclin 1 Supports Autophagosome Biogenesis in the Absence of ULK1 and ULK2 Kinases

1
Molecular and Integrative Biosciences Research Programme, University of Helsinki, 00014 Helsinki, Finland
2
Institute of Biotechnology & HiLIFE, University of Helsinki, 00014 Helsinki, Finland
3
Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland
4
Department of Biomedical and Molecular Sciences and Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON K7L 3N6, Canada
5
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK
6
Institute of Biomedicine, University of Turku, 20520 Turku, Finland
*
Author to whom correspondence should be addressed.
Cells 2019, 8(5), 475; https://doi.org/10.3390/cells8050475
Received: 24 April 2019 / Revised: 10 May 2019 / Accepted: 15 May 2019 / Published: 17 May 2019
(This article belongs to the Special Issue Autophagy in Neurodegenerative Diseases)
Autophagy transports cytoplasmic material and organelles to lysosomes for degradation and recycling. Beclin 1 forms a complex with several other autophagy proteins and functions in the initiation phase of autophagy, but the exact role of Beclin 1 subcellular localization in autophagy initiation is still unclear. In order to elucidate the role of Beclin 1 localization in autophagosome biogenesis, we generated constructs that target Beclin 1 to the endoplasmic reticulum (ER) or mitochondria. Our results confirmed the proper organelle-specific targeting of the engineered Beclin 1 constructs, and the proper formation of autophagy-regulatory Beclin 1 complexes. The ULK kinases are required for autophagy initiation upstream of Beclin 1, and autophagosome biogenesis is severely impaired in ULK1/ULK2 double knockout cells. We tested whether Beclin 1 targeting facilitated its ability to rescue autophagosome formation in ULK1/ULK2 double knockout cells. ER-targeted Beclin 1 was most effective in the rescue experiments, while mitochondria-targeted and non-targeted Beclin 1 also showed an ability to rescue, but with lower activity. However, none of the constructs was able to increase autophagic flux in the knockout cells. We also showed that wild type Beclin 1 was enriched on the ER during autophagy induction, and that ULK1/ULK2 facilitated the ER-enrichment of Beclin 1 under basal conditions. The results suggest that one of the functions of ULK kinases may be to enhance Beclin 1 recruitment to the ER to drive autophagosome formation. View Full-Text
Keywords: autophagy; Beclin 1; ULK1; ULK2; endoplasmic reticulum; mitochondria autophagy; Beclin 1; ULK1; ULK2; endoplasmic reticulum; mitochondria
Show Figures

Figure 1

MDPI and ACS Style

Anwar, T.; Liu, X.; Suntio, T.; Marjamäki, A.; Biazik, J.; Chan, E.Y.W.; Varjosalo, M.; Eskelinen, E.-L. ER-Targeted Beclin 1 Supports Autophagosome Biogenesis in the Absence of ULK1 and ULK2 Kinases. Cells 2019, 8, 475.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop