Interactions between mitochondrial bioenergetics and cytoplasmic calcium in cultured cerebellar granule cells.
The mitochondrion has moved to the center stage in the drama of the life and death of the neuron. The mitochondrial membrane potential controls the ability of the organelle to generate ATP, generate reactive oxygen species and sequester Ca(2+) entering the cell. Each of these processes interact, and their deconvolution is far from trivial. The cultured cerebellar granule cell provides a model in which knowledge gained from studies on isolated mitochondria can be applied to study the role played by the organelles in the maintenance of Ca(2+) homeostasis in the cell under resting, stimulated and pathophysiological conditions. In particular, mitochondria play a complex role in the response of the neuron to excitotoxic stimulation of NMDA and AMPA-kainate selective glutamate receptors. One goal of research in this area is to provide clues as to possible ways in which modulators of mitochondrial function may be used as neuroprotective agents, since mitochondrial Ca(2+) accumulation seems to play a key role in glutamate excitotoxicity.
Nicholls
David G
DG
Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA. dnicholls@Buckininstitute.org
Vesce
Sabino
S
Kirk
Liana
L
Chalmers
Susan
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009840:Oligomycins / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D019289:Pyruvic Acid / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D014475:Uncoupling Agents / Q000494:pharmacology
D000255:Adenosine Triphosphate; D002118:Calcium; D018698:Glutamic Acid; D009840:Oligomycins; D019289:Pyruvic Acid; D017382:Reactive Oxygen Species; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D014475:Uncoupling Agents