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Physiol. Rev. 80: 315-360, 2000;
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Physiological Reviews, Vol. 80, No. 1, January 2000, pp. 315-360
Copyright ©2000 by the American Physiological Society

Mitochondria and Neuronal Survival

David G. Nicholls and Samantha L. Budd

Department of Pharmacology and Neuroscience, University of Dundee, Dundee, Scotland; and Cerebrovascular and Neuroscience Research Institute, Brigham and Women's Hospital, Boston, Massachusetts

Nicholls, David G. and Samantha L. Budd. Mitochondria and Neuronal Survival. Physiol. Rev. 80: 315-360, 2000.Mitochondria play a central role in the survival and death of neurons. The detailed bioenergetic mechanisms by which isolated mitochondria generate ATP, sequester Ca2+, generate reactive oxygen species, and undergo Ca2+-dependent permeabilization of their inner membrane are currently being applied to the function of mitochondria in situ within neurons under physiological and pathophysiological conditions. Here we review the functional bioenergetics of isolated mitochondria, with emphasis on the chemiosmotic proton circuit and the application (and occasional misapplication) of these principles to intact neurons. Mitochondria play an integral role in both necrotic and apoptotic neuronal cell death, and the bioenergetic principles underlying current studies are reviewed.




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Mitochondrial Regulation of Synaptic Plasticity in the Hippocampus
J. Biol. Chem., May 9, 2003; 278(20): 17727 - 17734.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
V. P. Bindokas, A. Kuznetsov, S. Sreenan, K. S. Polonsky, M. W. Roe, and L. H. Philipson
Visualizing Superoxide Production in Normal and Diabetic Rat Islets of Langerhans
J. Biol. Chem., March 7, 2003; 278(11): 9796 - 9801.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
J. Niquet, R. A. Baldwin, S. G. Allen, D. G. Fujikawa, and C. G. Wasterlain
Hypoxic neuronal necrosis: Protein synthesis-independent activation of a cell death program
PNAS, March 4, 2003; 100(5): 2825 - 2830.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
J. Nilsen and R. D. Brinton
Mechanism of estrogen-mediated neuroprotection: Regulation of mitochondrial calcium and Bcl-2 expression
PNAS, March 4, 2003; 100(5): 2842 - 2847.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
I. F. Smith, J. P. Boyle, L. D. Plant, H. A. Pearson, and C. Peers
Hypoxic Remodeling of Ca2+ Stores in Type I Cortical Astrocytes
J. Biol. Chem., February 7, 2003; 278(7): 4875 - 4881.
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 J. Neurosci.Home page
N. B. Pivovarova, L. D. Pozzo-Miller, J. Hongpaisan, and S. B. Andrews
Correlated Calcium Uptake and Release by Mitochondria and Endoplasmic Reticulum of CA3 Hippocampal Dendrites after Afferent Synaptic Stimulation
J. Neurosci., December 15, 2002; 22(24): 10653 - 10661.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
J. Xiong, A. Verkhratsky, and E. C. Toescu
Changes in Mitochondrial Status Associated with Altered Ca2+ Homeostasis in Aged Cerebellar Granule Neurons in Brain Slices
J. Neurosci., December 15, 2002; 22(24): 10761 - 10771.
[Abstract] [Full Text] [PDF]

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 J. Neurophysiol.Home page
R. Kovacs, S. Schuchmann, S. Gabriel, O. Kann, J. Kardos, and U. Heinemann
Free Radical-Mediated Cell Damage After Experimental Status Epilepticus in Hippocampal Slice Cultures
J Neurophysiol, December 1, 2002; 88(6): 2909 - 2918.
[Abstract] [Full Text] [PDF]

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 StrokeHome page
A.A. Mongin, H. Bolay, and T. Dalkara
Nitric Oxide May Contribute to the Long-Term Impairment of Synaptic Transmission After Transient Ischemia
Stroke, October 1, 2002; 33(10): 2348 - 2350.
[Full Text] [PDF]

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 StrokeHome page
L. D. Plant, P. J. Kemp, C. Peers, Z. Henderson, and H. A. Pearson
Hypoxic Depolarization of Cerebellar Granule Neurons by Specific Inhibition of TASK-1
Stroke, September 1, 2002; 33(9): 2324 - 2328.
[Abstract] [Full Text] [PDF]

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 JCBHome page
E. Werner and Z. Werb
Integrins engage mitochondrial function for signal transduction by a mechanism dependent on Rho GTPases
J. Cell Biol., July 22, 2002; 158(2): 357 - 368.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
B. Billups and I. D. Forsythe
Presynaptic Mitochondrial Calcium Sequestration Influences Transmission at Mammalian Central Synapses
J. Neurosci., July 15, 2002; 22(14): 5840 - 5847.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
E. J. Weeber, M. Levy, M. J. Sampson, K. Anflous, D. L. Armstrong, S. E. Brown, J. D. Sweatt, and W. J. Craigen
The Role of Mitochondrial Porins and the Permeability Transition Pore in Learning and Synaptic Plasticity
J. Biol. Chem., May 17, 2002; 277(21): 18891 - 18897.
[Abstract] [Full Text] [PDF]

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 StrokeHome page
H. Bolay, Y. Gursoy-Ozdemir, Y. Sara, R. Onur, A. Can, and T. Dalkara
Persistent Defect in Transmitter Release and Synapsin Phosphorylation in Cerebral Cortex After Transient Moderate Ischemic Injury
Stroke, May 1, 2002; 33(5): 1369 - 1375.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
M. F. Lopez and S. Melov
Applied Proteomics: Mitochondrial Proteins and Effect on Function
Circ. Res., March 8, 2002; 90(4): 380 - 389.
[Abstract] [Full Text] [PDF]

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 StrokeHome page
N. J. Solenski, C. G. diPierro, P. A. Trimmer, A.-L. Kwan, and G. A. Helms
Ultrastructural Changes of Neuronal Mitochondria After Transient and Permanent Cerebral Ischemia
Stroke, March 1, 2002; 33(3): 816 - 824.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
M Inoue, N Fujishiro, I Imanaga, and Y Sakamoto
Role of ATP decrease in secretion induced by mitochondrial dysfunction in guinea-pig adrenal chromaffin cells
J. Physiol., February 15, 2002; 539(1): 145 - 155.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
D. Jiang, P. G. Sullivan, S. L. Sensi, O. Steward, and J. H. Weiss
Zn2+ Induces Permeability Transition Pore Opening and Release of Pro-apoptotic Peptides from Neuronal Mitochondria
J. Biol. Chem., December 7, 2001; 276(50): 47524 - 47529.
[Abstract] [Full Text] [PDF]

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 J Biomol ScreenHome page
A. J. Woollacott and P. B. Simpson
High Throughput Fluorescence Assays for the Measurement of Mitochondrial Activity in Intact Human Neuroblastoma Cells
J Biomol Screen, December 1, 2001; 6(6): 413 - 420.
[Abstract] [PDF]

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 Am. J. Neuroradiol.Home page
L. P. Mark, R. W. Prost, J. L. Ulmer, M. M. Smith, D. L. Daniels, J. M. Strottmann, W. D. Brown, and L. Hacein-Bey
Pictorial Review of Glutamate Excitotoxicity: Fundamental Concepts for Neuroimaging
AJNR Am. J. Neuroradiol., November 1, 2001; 22(10): 1813 - 1824.
[Full Text] [PDF]

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 Sci Aging Knowl EnvironHome page
J. K. Andersen, J. Kumar, B. Srinivas, D. Kaur, M. Hsu, and S. Rajagopalan
The Hunt for a Cure for Parkinson's Disease
Sci. Aging Knowl. Environ., October 3, 2001; 2001(1): re1 - 1.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
J. F. Buckman and I. J. Reynolds
Spontaneous Changes in Mitochondrial Membrane Potential in Cultured Neurons
J. Neurosci., July 15, 2001; 21(14): 5054 - 5065.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
J. B Brocard, M. Tassetto, and I. J Reynolds
Quantitative evaluation of mitochondrial calcium content in rat cortical neurones following a glutamate stimulus
J. Physiol., March 15, 2001; 531(3): 793 - 805.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
D. Ricquier and F. Bouillaud
Mitochondrial uncoupling proteins: from mitochondria to the regulation of energy balance
J. Physiol., November 15, 2000; 529(1): 3 - 10.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
G. Hajnoczky, G. Csordas, M. Madesh, and P. Pacher
The machinery of local Ca2+ signalling between sarco-endoplasmic reticulum and mitochondria
J. Physiol., November 15, 2000; 529(1): 69 - 81.
[Abstract] [Full Text] [PDF]

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 JGPHome page
S. V. Straub, D. R. Giovannucci, and D. I. Yule
Calcium Wave Propagation in Pancreatic Acinar Cells: Functional Interaction of Inositol 1,4,5-Trisphosphate Receptors, Ryanodine Receptors, and Mitochondria
J. Gen. Physiol., October 1, 2000; 116(4): 547 - 560.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
M. W. Ward, A. C. Rego, B. G. Frenguelli, and D. G. Nicholls
Mitochondrial Membrane Potential and Glutamate Excitotoxicity in Cultured Cerebellar Granule Cells
J. Neurosci., October 1, 2000; 20(19): 7208 - 7219.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
J. Lotharius and K. L. O'Malley
The Parkinsonism-inducing Drug 1-Methyl-4-phenylpyridinium Triggers Intracellular Dopamine Oxidation. A NOVEL MECHANISM OF TOXICITY
J. Biol. Chem., December 1, 2000; 275(49): 38581 - 38588.
[Abstract] [Full Text] [PDF]


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