RGD Reference Report - Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak. - Rat Genome Database

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Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak.

Authors: Majewski, N  Nogueira, V  Bhaskar, P  Coy, PE  Skeen, JE  Gottlob, K  Chandel, NS  Thompson, CB  Robey, RB  Hay, N 
Citation: Majewski N, etal., Mol Cell 2004 Dec 3;16(5):819-30.
RGD ID: 1358232
Pubmed: (View Article at PubMed) PMID:15574336
DOI: Full-text: DOI:10.1016/j.molcel.2004.11.014

The serine/threonine kinase Akt inhibits mitochondrial cytochrome c release and apoptosis induced by a variety of proapoptotic stimuli. The antiapoptotic activity of Akt is coupled, at least in part, to its effects on cellular metabolism. Here, we provide genetic evidence that Akt is required to maintain hexokinase association with mitochondria. Targeted disruption of this association impairs the ability of growth factors and Akt to inhibit cytochrome c release and apoptosis. Targeted disruption of mitochondria-hexokinase (HK) interaction or exposure to proapoptotic stimuli that promote rapid dissociation of hexokinase from mitochondria potently induce cytochrome c release and apoptosis, even in the absence of Bax and Bak. These effects are inhibited by activated Akt, but not by Bcl-2, implying that changes in outer mitochondrial membrane (OMM) permeability leading to apoptosis can occur in the absence of Bax and Bak and that Akt inhibits these changes through maintenance of hexokinase association with mitochondria.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Hk1  (hexokinase 1)

Objects referenced in this article
Gene Akt1 AKT serine/threonine kinase 1 Rattus norvegicus
Gene Bak1 BCL2-antagonist/killer 1 Rattus norvegicus
Gene Bax BCL2 associated X, apoptosis regulator Rattus norvegicus
Gene Hk2 hexokinase 2 Rattus norvegicus

Additional Information