De novo phosphatidylcholine synthesis is required for autophagosome membrane formation and maintenance during autophagy.

De novo phosphatidylcholine synthesis is required for autophagosome membrane formation and maintenance during autophagy. Autophagy. 2019 Sep 13;:1-17 Authors: Andrejeva G, Gowan S, Lin G, Wong Te Fong AL, Shamsaei E, Parkes HG, Mui J, Raynaud FI, Asad Y, Vizcay-Barrena G, Nikitorowicz-Buniak J, Valenti M, Howell L, Fleck RA, Martin LA, Kirkin V, Leach MO, Chung YL Abstract Macroautophagy/autophagy can enable cancer cells to withstand cellular stress and maintain bioenergetic homeostasis by sequestering cellular components into newly formed double-membrane vesicles destined for lysosomal degradation, potentially affecting the efficacy of anti-cancer treatments. Using 13C-labeled choline and 13C-magnetic resonance spectroscopy and western blotting, we show increased de novo choline phospholipid (ChoPL) production and activation of PCYT1A (phosphate cytidylyltransferase 1, choline, alpha), the rate-limiting enzyme of phosphatidylcholine (PtdCho) synthesis, during autophagy. We also discovered that the loss of PCYT1A activity results in compromised autophagosome formation and maintenance in autophagic cells. Direct tracing of ChoPLs with fluorescence and immunogold labeling imaging revealed the incorporation of newly synthesized ChoPLs into autophagosomal membranes, endoplasmic reticulum (ER) and mitochondria during anticancer drug-induced autophagy. Significant increase in the colocalization of fluorescence signals from the newly synthe...
Source: Autophagy - Category: Cytology Authors: Tags: Autophagy Source Type: research