Hexokinase 1 forms rings that regulate mitochondrial fission during energy stress
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Erişim
info:eu-repo/semantics/openAccessTarih
2024Yazar
Pilic, JohannesGottschalk, Benjamin
Bourgeois, Benjamin
Habisch, Hansjörg
Koshenov, Zhanat
Oflaz, Furkan Enes
Erdoğan, Yusuf Can
Miri, Seyed Mohammad
Yiğit, Esra Nur
Aydın, Mehmet Şerif
Öztürk, Gürkan
Eroğlu, Emrah
Shoshan Barmatz, Varda
Madl, Tobias
Graier, Wolfgang F.
Malli, Roland
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Pilic, J., Gottschalk, B., Bourgeois, B., Habisch, H., Koshenov, Z., Oflaz, F. E. ... Malli, R. (2024). Hexokinase 1 forms rings that regulate mitochondrial fission during energy stress. Molecular Cell, 84, 1-15. http://dx.doi.org/10.1016/j.molcel.2024.06.009Özet
Metabolic enzymes can adapt during energy stress, but the consequences of these adaptations remain understudied. Here, we discovered that hexokinase 1 (HK1), a key glycolytic enzyme, forms rings around mitochondria during energy stress. These HK1-rings constrict mitochondria at contact sites with the endoplasmic reticulum (ER) and mitochondrial dynamics protein (MiD51). HK1-rings prevent mitochondrial fission by displacing the dynamin-related protein 1 (Drp1) from mitochondrial fission factor (Mff) and mitochondrial fission 1 protein (Fis1). The disassembly of HK1-rings during energy restoration correlated with mitochondrial fission. Mechanistically, we identified that the lack of ATP and glucose-6-phosphate (G6P) promotes the formation of HK1-rings. Mutations that affect the formation of HK1-rings showed that HK1-rings rewire cellular metabolism toward increased TCA cycle activity. Our findings highlight that HK1 is an energy stress sensor that regulates the shape, connectivity, and metabolic activity of mitochondria. Thus, the formation of HK1-rings may affect mitochondrial function in energy-stress-related pathologies.
Kaynak
Molecular CellCilt
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