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SHR Neuro Cancer Cardio Lipid Metab Microb
Pilic, J; Gottschalk, B; Bourgeois, B; Habisch, H; Koshenov, Z; Oflaz, FE; Erdogan, YC; Miri, SM; Yiğit, EN; Aydın, MŞ; Öztürk, G; Eroglu, E; Shoshan-Barmatz, V; Madl, T; Graier, WF; Malli, R.
Hexokinase 1 forms rings that regulate mitochondrial fission during energy stress.
Mol Cell. 2024; 84(14): 2732-2746.e5.
Doi: 10.1016/j.molcel.2024.06.009
Web of Science
PubMed
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FullText_MUG
- Leading authors Med Uni Graz
- Malli Roland
- Pilic Johannes
- Co-authors Med Uni Graz
- Bourgeois Benjamin Michel Rene
- Erdogan Yusuf Ceyhun
- EROGLU Emrah
- Gottschalk Benjamin
- Graier Wolfgang
- Habisch Hansjörg
- Koshenov Zhanat
- Madl Tobias
- Oflaz Furkan Enes
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Hexokinase - metabolism, genetics
- Mitochondrial Dynamics - administration & dosage
- Humans - administration & dosage
- Mitochondria - metabolism, genetics, enzymology
- Energy Metabolism - administration & dosage
- Dynamins - metabolism, genetics
- Mitochondrial Proteins - metabolism, genetics
- Animals - administration & dosage
- Adenosine Triphosphate - metabolism
- Stress, Physiological - administration & dosage
- Endoplasmic Reticulum - metabolism
- Membrane Proteins - metabolism, genetics
- Citric Acid Cycle - administration & dosage
- Glucose-6-Phosphate - metabolism
- Mice - administration & dosage
- HeLa Cells - administration & dosage
- HEK293 Cells - administration & dosage
- GTP Phosphohydrolases - metabolism, genetics
- Mutation - administration & dosage