Selected Publication:

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 FullText 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

Altmetrics:

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

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

© Med Uni Graz • Imprint