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Plasma membrane calcium pump regulation by metabolic stress

Plasma membrane calcium pump regulation by metabolic stress
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摘要 The plasma membrane Ca2+-ATPase(PMCA)is an ATPdriven pump that is critical for the maintenance of low resting[Ca2+]i in all eukaryotic cells.Metabolic stress, either due to inhibition of mitochondrial or glycolytic metabolism,has the capacity to cause ATP depletion and thus inhibit PMCA activity.This has potentially fatal consequences,particularly for non-excitable cells in which the PMCA is the major Ca2+efflux pathway.This is because inhibition of the PMCA inevitably leads to cytosolic Ca2+ overload and the consequent cell death.However,the relationship between metabolic stress,ATP depletion and inhibition of the PMCA is not as simple as one would have originally predicted.There is increasing evidence that metabolic stress can lead to the inhibition of PMCA activity independent of ATP or prior to substantial ATP depletion.In particular,there is evidence that the PMCA has its own glycolytic ATP supply that can fuel the PMCA in the face of impaired mitochondrial function.Moreover, membrane phospholipids,mitochondrial membrane potential,caspase/calpain cleavage and oxidative stress have all been implicated in metabolic stress-induced inhibition of the PMCA.The major focus of this review is to challenge the conventional view of ATP-dependent regulation of the PMCA and bring together some of the alternative or additional mechanisms by which metabolic stress impairs PMCA activity resulting in cytosolic Ca2+ overload and cytotoxicity. The plasma membrane Ca2+-ATPase (PMCA) is an ATP-driven pump that is critical for the maintenance of low resting [Ca2+]i in all eukaryotic cells. Metabolic stress, either due to inhibition of mitochondrial or glycolytic metabolism, has the capacity to cause ATP depletion and thus inhibit PMCA activity. This has potentially fatal consequences, particularly for non-excitable cells in which the PMCA is the major Ca2+ efflux pathway. This is because inhibition of the PMCA inevitably leads to cytosolic Ca2+ overload and the consequent cell death. However, the relationship between metabolic stress, ATP depletion and inhibition of the PMCA is not as simple as one would have originally predicted. There is increasing evidence that metabolic stress can lead to the inhibition of PMCA activity independent of ATP or prior to substantial ATP depletion. In particular, there is evidence that the PMCA has its own glycolytic ATP supply that can fuel the PMCA in the face of impaired mitochondrial function. Moreover, membrane phospholipids, mitochondrial membrane potential, caspase/calpain cleavage and oxidative stress have all been implicated in metabolic stress-induced inhibition of the PMCA. The major focus of this review is to challenge the conventional view of ATP-dependent regulation of the PMCA and bring together some of the alternative or additional mechanisms by which metabolic stress impairs PMCA activity resulting in cytosolic Ca2+ overload and cytotoxicity.
出处 《World Journal of Biological Chemistry》 CAS 2010年第7期221-228,共8页 世界生物化学杂志(英文版)(电子版)
基金 Supported by A New Investigator Award from the BBSRC
关键词 Plasma membrane Ca 2+ -ATPase CALCIUM OVERLOAD METABOLIC stress CALCIUM PUMP MITOCHONDRIA Plasma membrane Ca2+-ATPase Calcium overload Metabolic stress Calcium pump Mitochondria
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  • 1Criddle DN,Murphy J,Fistetto G,Barrow S,Tepikin AV,Neoptolemos JP,et al.Fatty acid ethyl esters cause pancreatic calcium toxicity via inositol trisphosphate receptors and loss of ATP synthesis. Gastroenterology . 2006
  • 2Madhav,Bhatia.Apoptosis versus necrosis in acute pancreatitis. American Journal of Physiology-Gastrointestinal and Liver Physiology . 2004

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