ATP-driven and AMPK-independent autophagy in an early branching eukaryotic parasite

Feng-Jun Li, Zhi-Shen Xu, Andy D. S. Soo, Zhao-Rong Lun, and Cynthia Y. He.

Autophagy. 2017 Apr 3;13(4):715-729.

Speaker: Pin-Ju Ko (柯品如)                                           Time: 14:00~15:00, Jan. 10, 2017

Commentator: Dr. Jyh-Wei, Shin (辛致煒老師)         Place: Room 601

Abstract:

Autophagy is a pathway that support cell survival under starvation or other stress conditions, including glucose and amino acids have been extensively studied.¹ The AMP-activated protein kinase (AMPK) senses low energy levels in cells, that usually occur upon glucose depletion, but the exact role of glucose in autophagy is still controversial. Also, amino acid deprivation has been reported in different models, but cellular ATP levels under amino acid starvation was rarely investigated. However, autophagy studies are much less  known in the parasite. The early-branching protozoan Trypanosoma brucei transmits between mammal hosts via tsetse flies, when encountered distinct host environments with varying conditions, cells undergo extensive remodeling in their cellular metabolic pathways in different hosts, the bloodstream form (BSF) and procyclic form (PCF) trypanosomes. By using this well-defined energy metabolism pathways in T. brucei, authors systematically analyzed the relationship between energy metabolism and autophagy. They demonstrated that cellular ATP production is enhanced upon amino acid starvation and autophagic activity positively correlates with cellular ATP level in both PCF and BSF cells. Base on the knowledge about how the BSF and PCF generate energy,^2,3 they found out that blocking glucose or proline metabolism inhibits autophagy in an ATP-dependent mode. Here also showed that glucose starvation could not induce autophagy and AMPK was dispensable in amino acid starvation-induced autophagy, suggesting T. brucei lack of an autophagy signaling mechanism through sensing of low energy charge. In summary, these findings indicated a positive correlation between cellular energy level and autophagy, and emphasized the critical role of ATP production in determining autophagy activity.

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2.      van Weelden SW, Fast B, Vogt A, van der Meer P, Saas J, van Hellemond JJ, Tielens AG, Boshart M. Procyclic Trypanosoma brucei do not use Krebs cycle activity for energy generation. J Biol Chem 2003; 278:12854-63.

3.      Lamour N, Riviere L, Coustou V, Coombs GH, Barrett MP, Bringaud F. Proline metabolism in procyclic Trypanosoma brucei is down-regulated in the presence of glucose. J Biol Chem 2005; 280:11902-10.