Abstract
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.
| Original language | English |
|---|---|
| Article number | e0193182 |
| Journal | PloS one |
| Volume | 13 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2018 Feb |
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All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
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Hexokinase 2 is a molecular bridge linking telomerase and autophagy. / Roh, Jae Il; Kim, Yujin; Oh, Jahyun; Kim, Yunmi; Lee, Jeehyun; Lee, Jaehoon; Chun, Kyung Hee; Lee, Han Woong.
In: PloS one, Vol. 13, No. 2, e0193182, 02.2018.Research output: Contribution to journal › Article
TY - JOUR
T1 - Hexokinase 2 is a molecular bridge linking telomerase and autophagy
AU - Roh, Jae Il
AU - Kim, Yujin
AU - Oh, Jahyun
AU - Kim, Yunmi
AU - Lee, Jeehyun
AU - Lee, Jaehoon
AU - Chun, Kyung Hee
AU - Lee, Han Woong
PY - 2018/2
Y1 - 2018/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85042441607&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042441607&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0193182
DO - 10.1371/journal.pone.0193182
M3 - Article
C2 - 29462198
AN - SCOPUS:85042441607
VL - 13
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 2
M1 - e0193182
ER -