Lipid droplet and early autophagosomal membrane targeting of Atg2A and Atg14L in human tumor cells.

Pfisterer, Simon G; Bakula, Daniela; Frickey, Tancred; Cezanne, Alice; Brigger, Daniel; Tschan, Mario; Robenek, Horst; Proikas-Cezanne, Tassula (2014). Lipid droplet and early autophagosomal membrane targeting of Atg2A and Atg14L in human tumor cells. Journal of lipid research, 55(7), pp. 1267-1278. American Society for Biochemistry and Molecular Biology ASBMB 10.1194/jlr.M046359

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Autophagy is a lysosomal bulk degradation pathway for cytoplasmic cargo, such as long-lived proteins, lipids, and organelles. Induced upon nutrient starvation, autophagic degradation is accomplished by the concerted actions of autophagy-related (ATG) proteins. Here we demonstrate that two ATGs, human Atg2A and Atg14L, colocalize at cytoplasmic lipid droplets (LDs) and are functionally involved in controlling the number and size of LDs in human tumor cell lines. We show that Atg2A is targeted to cytoplasmic ADRP-positive LDs that migrate bidirectionally along microtubules. The LD localization of Atg2A was found to be independent of the autophagic status. Further, Atg2A colocalized with Atg14L under nutrient-rich conditions when autophagy was not induced. Upon nutrient starvation and dependent on phosphatidylinositol 3-phosphate [PtdIns(3)P] generation, both Atg2A and Atg14L were also specifically targeted to endoplasmic reticulum-associated early autophagosomal membranes, marked by the PtdIns(3)P effectors double-FYVE containing protein 1 (DFCP1) and WD-repeat protein interacting with phosphoinositides 1 (WIPI-1), both of which function at the onset of autophagy. These data provide evidence for additional roles of Atg2A and Atg14L in the formation of early autophagosomal membranes and also in lipid metabolism.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Med. Onkologie / Hämatologie (Erw.)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Med. Onkologie / Hämatologie (Erw.)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Brigger, Daniel and Tschan, Mario

ISSN:

0022-2275

Publisher:

American Society for Biochemistry and Molecular Biology ASBMB

Language:

English

Submitter:

Doris Haefelin

Date Deposited:

27 Feb 2015 14:02

Last Modified:

02 Feb 2016 10:55

Publisher DOI:

10.1194/jlr.M046359

PubMed ID:

24776541

Uncontrolled Keywords:

Atg14L, Atg2A, WIPI-1, autophagosome, autophagy, double-FYVE containing protein 1

BORIS DOI:

10.7892/boris.63854

URI:

https://boris.unibe.ch/id/eprint/63854

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