Bcl-XL maintains mitochondrial function in murine astrocytes deprived of glucose.

Bcl-XL is a protein that blocks both apoptotic and necrotic cell death. The authors have previously shown that it is effective in maintaining mitochondrial membrane potential during glucose deprivation in cultured astrocytes. To further investigate the mechanism involved, the authors studied mitochondrial function and cytochrome c release. Oxygen consumption was monitored to assess oxidative respiration. State III respiration decreased significantly as early as 3 h after removal of glucose. At this time mitochondria hyperpolarize but cytochrome c is not yet released. Damage to the electron transport chain is not responsible for this change because uncoupled respiration was unchanged at this time point. At 5 h of glucose deprivation, when mitochondrial depolarization was observed, state IV respiration increased significantly, cytochrome c began to be released, and mitochondrial morphology changed from elongated to punctate. When Bcl-XL was overexpressed normal state III respiration and mitochondrial morphology were maintained and cytochrome c release was inhibited in the face of glucose deprivation stress.