BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis

Speaker: 林婷鈺

Commentator: 蔣輯武老師

Time: 11/05/2003 14:00~15:00

Place: 601教室

Abstract:

  BAD, a BH3-only protein of the Bcl-2 protein family, is regulated in response to extracellular survival or death signals and serves as a molecular sentinel to trigger apoptosis (1). Glucokinase, a member of the hexokinase family exists in liver cells and pancreatic β cells, is essential for the unique metabolic functions of these tissues to catalyze the first step in glycolyisis (2). In mammalian cells, glycolysis and apoptosis are considered major but independent pathways that are critical for cell survival.The authors used a proteomic approach to find out that BAD is present in a functional multi-protein complex together with protein kinase A, protein phosphatase 1 catalytic units, Wiskott–Aldrich family member WAVE-1 and glucokinase in liver mitochondria. BAD is crucial for the formation of the glucokinase-containing complex, and this complex is responsible for phosphorylating glucose to produce glucose 6-phosphate. Phosphorylation status of BAD helps to regulate glucokinase activity, and glucose deprivation results in dephosphorylation of BAD (3). This study suggests that BAD regulates glucose metabolism and mediates apoptosis induced by glucose deprivation.

References:

1.         Harada, h. et al. Phosphorylation and inactivation of BAD by mitochondria-anchored protein kinase A. Mol. Cell 3: 413-422, 1999.

2.         Postic, C. et al. Cell-specific roles of glucokinase in glucose homeostasis. Recent Prog. Horm. Res. 56: 195-217, 2001.

3.         Danial, N. N. et al. BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature 424: 952-956, 2003.