BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis
- PMID: 12931191
- DOI: 10.1038/nature01825
BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis
Abstract
Glycolysis and apoptosis are considered major but independent pathways that are critical for cell survival. The activity of BAD, a pro-apoptotic BCL-2 family member, is regulated by phosphorylation in response to growth/survival factors. Here we undertook a proteomic analysis to assess whether BAD might also participate in mitochondrial physiology. In liver mitochondria, BAD resides in a functional holoenzyme complex together with protein kinase A and protein phosphatase 1 (PP1) catalytic units, Wiskott-Aldrich family member WAVE-1 as an A kinase anchoring protein, and glucokinase (hexokinase IV). BAD is required to assemble the complex in that Bad-deficient hepatocytes lack this complex, resulting in diminished mitochondria-based glucokinase activity and blunted mitochondrial respiration in response to glucose. Glucose deprivation results in dephosphorylation of BAD, and BAD-dependent cell death. Moreover, the phosphorylation status of BAD helps regulate glucokinase activity. Mice deficient for BAD or bearing a non-phosphorylatable BAD(3SA) mutant display abnormal glucose homeostasis including profound defects in glucose tolerance. This combination of proteomics, genetics and physiology indicates an unanticipated role for BAD in integrating pathways of glucose metabolism and apoptosis.
Comment in
-
Cell biology: metabolism meets death.Nature. 2003 Aug 21;424(6951):896-7. doi: 10.1038/424896a. Nature. 2003. PMID: 12931174 No abstract available.
Similar articles
-
Molecular modeling of BAD complex resided in a mitochondrion integrating glycolysis and apoptosis.J Theor Biol. 2010 Sep 21;266(2):231-41. doi: 10.1016/j.jtbi.2010.06.009. Epub 2010 Jun 9. J Theor Biol. 2010. PMID: 20540951
-
BAD: undertaker by night, candyman by day.Oncogene. 2008 Dec;27 Suppl 1:S53-70. doi: 10.1038/onc.2009.44. Oncogene. 2008. PMID: 19641507 Review.
-
Glucokinase regulatory protein is associated with mitochondria in hepatocytes.FEBS Lett. 2006 Apr 3;580(8):2065-70. doi: 10.1016/j.febslet.2006.03.009. Epub 2006 Mar 10. FEBS Lett. 2006. PMID: 16542652
-
Role of JNK activation in apoptosis: a double-edged sword.Cell Res. 2005 Jan;15(1):36-42. doi: 10.1038/sj.cr.7290262. Cell Res. 2005. PMID: 15686625 Review.
-
Cell biology: metabolism meets death.Nature. 2003 Aug 21;424(6951):896-7. doi: 10.1038/424896a. Nature. 2003. PMID: 12931174 No abstract available.
Cited by
-
Site-Specifically Modified Peptide Inhibitors of Protein Tyrosine Phosphatase 1B and T-Cell Protein Tyrosine Phosphatase with Enhanced Stability and Improved In Vivo Long-Acting Activity.ACS Pharmacol Transl Sci. 2024 Apr 24;7(5):1426-1437. doi: 10.1021/acsptsci.4c00054. eCollection 2024 May 10. ACS Pharmacol Transl Sci. 2024. PMID: 38751623
-
Phosphoproteomic analysis reveals changes in A-Raf-related protein phosphorylation in response to Toxoplasma gondii infection in porcine macrophages.Parasit Vectors. 2024 Apr 20;17(1):191. doi: 10.1186/s13071-024-06273-x. Parasit Vectors. 2024. PMID: 38643189 Free PMC article.
-
Hexokinase-linked glycolytic overload and unscheduled glycolysis in hyperglycemia-induced pathogenesis of insulin resistance, beta-cell glucotoxicity, and diabetic vascular complications.Front Endocrinol (Lausanne). 2024 Jan 16;14:1268308. doi: 10.3389/fendo.2023.1268308. eCollection 2023. Front Endocrinol (Lausanne). 2024. PMID: 38292764 Free PMC article.
-
Vertical pathway inhibition of receptor tyrosine kinases and BAD with synergistic efficacy in triple negative breast cancer.NPJ Precis Oncol. 2024 Jan 10;8(1):8. doi: 10.1038/s41698-023-00489-3. NPJ Precis Oncol. 2024. PMID: 38200104 Free PMC article.
-
Dysfunction of Drosophila mitochondrial carrier homolog (Mtch) alters apoptosis and disturbs development.FEBS Open Bio. 2024 Feb;14(2):276-289. doi: 10.1002/2211-5463.13742. Epub 2023 Dec 19. FEBS Open Bio. 2024. PMID: 38013241 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials