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Hexokinase 2 is a molecular bridge linking telomerase and autophagy

 Jae-il Roh  ;  Yujin Kim  ;  Jahyun Oh  ;  Yunmi Kim  ;  Jeehyun Lee  ;  Jaehoon Lee  ;  Kyung-Hee Chun  ;  Han-Woong Lee 
 PLOS ONE, Vol.13(2) : 0193182, 2018 
Journal Title
Issue Date
Autophagy/physiology* ; Glucose/metabolism ; Glycolysis/physiology ; HeLa Cells ; Hep G2 Cells ; Hexokinase/genetics ; Hexokinase/metabolism* ; Humans ; Promoter Regions, Genetic ; Telomerase/genetics ; Telomerase/metabolism*
Autophagy is systematically regulated by upstream factors and nutrients. Recent studies reported that telomerase and hexokinase 2 [HK2) regulate autophagy through mTOR and that telomerase has the capacity to bind to the HK2 promoter. However, the molecular linkage among telomerase, HK2, and autophagy is not fully understood. Here, we show that HK2 connects telomerase to autophagy. HK2 inhibition in HepG2 cells suppressed TERT-induced autophagy activation and further enhancement by glucose deprivation. The HK2 downstream factor mTOR was responsible for the TERT-induced autophagy activation under glucose deprivation, implying that TERT promotes autophagy through an HK2-mTOR pathway. TERC played a role similar to that of TERT, and simultaneous expression of TERT and TERC synergistically enhanced HK2 expression and autophagy. At the gene level, TERT bound to the HK2 promoter at a specific region harboring the telomerase-responsive sequence 'TTGGG.' Mutagenesis of TERC and the TERT-responsive element in the HK2 promoter revealed that TERC is required for the binding of TERT to the HK2 promoter. We demonstrate the existence of a telomerase-HK2-mTOR-autophagy axis and suggest that inhibition of the interaction between telomerase and the HK2 promoter diminishes glucose starvation-induced autophagy.
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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Chun, Kyung Hee(전경희) ORCID logo https://orcid.org/0000-0002-9867-7321
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