Investigation of the role of the glucose-6-phosphate translocase in the activation of autophagy and glycogen-selective autophagy in glycogen storage disease type IB patients
Аутори
Jocić, NikolaParezanović, Marina
Anđelković, Marina
Stevanović, Nina
Ugrin, Milena
Spasovski, Vesna
Klaassen, Kristel
Stanković, Sara
Komazec, Jovana
Pavlović, Sonja
Stojiljković, Maja
Skakić, Anita
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Introduction: Glycogen storage disease type Ib (GSD-Ib) is characterized by a deficiency of glucose-6-
phosphate translocase (G6PT) encoded by the SLC37A4 gene, affecting glucose homeostasis and disrupting autophagy. Recent findings suggest that G6PT may also play a role in autophagy and
glycogen-selective autophagy (glycophagy) activation independent of its transport function. To investigate this hypothesis, two groups of GSD-Ib patients carrying variants with different effects on G6PT
transport activity and stability (p.Asn27Lys and p.Leu348Valfs*53), were compared to the control group
of subjects.
Methods: The relative expression levels of SLC37A4 gene, autophagy (mTOR, ULK1, PRKAG1), and glycophagy markers(GABARAPL1, GAA, STBD1) were assessed in mononuclear cells of GSD Ib patients(four
carrying p.Asn27Lys and four carrying p.Leu348Valfs*53 variant) compared to control group using RTqPCR. Statistical analysis was performed using one-way ANOVA followed by a post-hoc t-test.
R...esults: The p.Asn27Lys group exhibited 1.5-2.5 times higher expression of SLC37A4 and autophagy
markers, while the p.Leu348Valfs*53 group showed downregulation by approximately 50% compared to
the control group. Glycophagy markers were increased twofold in both patient groups, except for GAA,
which had similar expression levels as the control group.
Conclusion: Individuals carrying the p.Asn27Lys variant display the presence of SLC37A4 transcript in
their cells, which correlates with autophagy activation. Conversely, in patients with the p.Leu348Valfs*53
variant SLC37A4 is downregulated, indicating compromised autophagy activation. These findings support the role of G6PT in autophagy activation, independent of itstransport activity. Furthermore, the elevated expression of glycophagy markers observed in both patient groups can be attributed to the
accumulated glycogen.
Кључне речи:
glycogen storage disease type Ib / glucose-6-phosphate translocase / autophagy / glycogen-selective autophagyИзвор:
CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia, 2023, 92-92Издавач:
- Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
Финансирање / пројекти:
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Jocić, Nikola AU - Parezanović, Marina AU - Anđelković, Marina AU - Stevanović, Nina AU - Ugrin, Milena AU - Spasovski, Vesna AU - Klaassen, Kristel AU - Stanković, Sara AU - Komazec, Jovana AU - Pavlović, Sonja AU - Stojiljković, Maja AU - Skakić, Anita PY - 2023 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2141 AB - Introduction: Glycogen storage disease type Ib (GSD-Ib) is characterized by a deficiency of glucose-6- phosphate translocase (G6PT) encoded by the SLC37A4 gene, affecting glucose homeostasis and disrupting autophagy. Recent findings suggest that G6PT may also play a role in autophagy and glycogen-selective autophagy (glycophagy) activation independent of its transport function. To investigate this hypothesis, two groups of GSD-Ib patients carrying variants with different effects on G6PT transport activity and stability (p.Asn27Lys and p.Leu348Valfs*53), were compared to the control group of subjects. Methods: The relative expression levels of SLC37A4 gene, autophagy (mTOR, ULK1, PRKAG1), and glycophagy markers(GABARAPL1, GAA, STBD1) were assessed in mononuclear cells of GSD Ib patients(four carrying p.Asn27Lys and four carrying p.Leu348Valfs*53 variant) compared to control group using RTqPCR. Statistical analysis was performed using one-way ANOVA followed by a post-hoc t-test. Results: The p.Asn27Lys group exhibited 1.5-2.5 times higher expression of SLC37A4 and autophagy markers, while the p.Leu348Valfs*53 group showed downregulation by approximately 50% compared to the control group. Glycophagy markers were increased twofold in both patient groups, except for GAA, which had similar expression levels as the control group. Conclusion: Individuals carrying the p.Asn27Lys variant display the presence of SLC37A4 transcript in their cells, which correlates with autophagy activation. Conversely, in patients with the p.Leu348Valfs*53 variant SLC37A4 is downregulated, indicating compromised autophagy activation. These findings support the role of G6PT in autophagy activation, independent of itstransport activity. Furthermore, the elevated expression of glycophagy markers observed in both patient groups can be attributed to the accumulated glycogen. PB - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade C3 - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia T1 - Investigation of the role of the glucose-6-phosphate translocase in the activation of autophagy and glycogen-selective autophagy in glycogen storage disease type IB patients EP - 92 SP - 92 UR - https://hdl.handle.net/21.15107/rcub_imagine_2141 ER -
@conference{ author = "Jocić, Nikola and Parezanović, Marina and Anđelković, Marina and Stevanović, Nina and Ugrin, Milena and Spasovski, Vesna and Klaassen, Kristel and Stanković, Sara and Komazec, Jovana and Pavlović, Sonja and Stojiljković, Maja and Skakić, Anita", year = "2023", abstract = "Introduction: Glycogen storage disease type Ib (GSD-Ib) is characterized by a deficiency of glucose-6- phosphate translocase (G6PT) encoded by the SLC37A4 gene, affecting glucose homeostasis and disrupting autophagy. Recent findings suggest that G6PT may also play a role in autophagy and glycogen-selective autophagy (glycophagy) activation independent of its transport function. To investigate this hypothesis, two groups of GSD-Ib patients carrying variants with different effects on G6PT transport activity and stability (p.Asn27Lys and p.Leu348Valfs*53), were compared to the control group of subjects. Methods: The relative expression levels of SLC37A4 gene, autophagy (mTOR, ULK1, PRKAG1), and glycophagy markers(GABARAPL1, GAA, STBD1) were assessed in mononuclear cells of GSD Ib patients(four carrying p.Asn27Lys and four carrying p.Leu348Valfs*53 variant) compared to control group using RTqPCR. Statistical analysis was performed using one-way ANOVA followed by a post-hoc t-test. Results: The p.Asn27Lys group exhibited 1.5-2.5 times higher expression of SLC37A4 and autophagy markers, while the p.Leu348Valfs*53 group showed downregulation by approximately 50% compared to the control group. Glycophagy markers were increased twofold in both patient groups, except for GAA, which had similar expression levels as the control group. Conclusion: Individuals carrying the p.Asn27Lys variant display the presence of SLC37A4 transcript in their cells, which correlates with autophagy activation. Conversely, in patients with the p.Leu348Valfs*53 variant SLC37A4 is downregulated, indicating compromised autophagy activation. These findings support the role of G6PT in autophagy activation, independent of itstransport activity. Furthermore, the elevated expression of glycophagy markers observed in both patient groups can be attributed to the accumulated glycogen.", publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade", journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia", title = "Investigation of the role of the glucose-6-phosphate translocase in the activation of autophagy and glycogen-selective autophagy in glycogen storage disease type IB patients", pages = "92-92", url = "https://hdl.handle.net/21.15107/rcub_imagine_2141" }
Jocić, N., Parezanović, M., Anđelković, M., Stevanović, N., Ugrin, M., Spasovski, V., Klaassen, K., Stanković, S., Komazec, J., Pavlović, S., Stojiljković, M.,& Skakić, A.. (2023). Investigation of the role of the glucose-6-phosphate translocase in the activation of autophagy and glycogen-selective autophagy in glycogen storage disease type IB patients. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 92-92. https://hdl.handle.net/21.15107/rcub_imagine_2141
Jocić N, Parezanović M, Anđelković M, Stevanović N, Ugrin M, Spasovski V, Klaassen K, Stanković S, Komazec J, Pavlović S, Stojiljković M, Skakić A. Investigation of the role of the glucose-6-phosphate translocase in the activation of autophagy and glycogen-selective autophagy in glycogen storage disease type IB patients. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:92-92. https://hdl.handle.net/21.15107/rcub_imagine_2141 .
Jocić, Nikola, Parezanović, Marina, Anđelković, Marina, Stevanović, Nina, Ugrin, Milena, Spasovski, Vesna, Klaassen, Kristel, Stanković, Sara, Komazec, Jovana, Pavlović, Sonja, Stojiljković, Maja, Skakić, Anita, "Investigation of the role of the glucose-6-phosphate translocase in the activation of autophagy and glycogen-selective autophagy in glycogen storage disease type IB patients" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):92-92, https://hdl.handle.net/21.15107/rcub_imagine_2141 .