Cited by 1,398Mitochondrial Function and PathologyCalcium signaling and nucleotide metabolismATP Synthase and ATPases Research

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Role of calcium ions in regulation of mammalian intramitochondrial metabolism

McCormack, J. G., Halestrap, A. P., Denton, R. M.·1990·Physiological Reviews

DOI 10.1152/physrev.1990.70.2.391

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Background
When is high‐Ca2+ microdomain required for mitochondrial Ca2+ uptake?*
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Background
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Zhou, L., Cabrera, M. E., Huang, H., Yuan, C. L., Duda, M. K., Sharma, N., Bian, F., & Stanley, W. C. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.123828 · Cited by 22
“2005b), indicating that Ca2+ stimulation of PDH phosphatase over-rides any activation of PDH kinase (McCormack et al. 1990).”
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Background
Calcium in suramin-induced rat sensory neuron toxicity in vitro
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“The currently accepted paradigm is that Ca directly modulates mitochondrial NADH levels via allosteric activation of matrix dehydrogenases [4,5,6,7], enhances ATP production via F1FO -ATPase activation [8,9], as well as, triggers a catastrophic phenomenon known as mitochondrial permeability transition [10,11,12].”
Background
Downregualtion of dynamin-related protein 1 attenuates glutamate-induced excitotoxicity via regulating mitochondrial function in a calcium dependent manner in HT22 cells
Zhang, C., Yuan, X., Li, H., Zhao, Z.-J., Liao, Y., Wang, X., Su, J., Sang, S., & Liu, Q. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.11.072 · Cited by 21
Estradiol affect Na-dependent Ca2+ efflux from synaptosomal mitochondria.
Horvat, A., Petrović, S., Nedeljković, N., Martinović, J. V., & Nikezić, G. (2000) · PubMed · Cited by 21
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“mitochondrial processes as pyridine nucleotide reduction (McCormack et al., 1990), ATP synthesis (Jouaville et al.”
BackgroundMethod
[Retracted] Protective Effect of Nicorandil on Cardiac Microvascular Injury: Role of Mitochondrial Integrity
Jiang, X., Wu, D., Jiang, Z., Ling, W., & Qian, G. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/4665632 · Cited by 23
Retracted
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Self-citation
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“To test whether altered calcium levels, a known activator of mitochondrial energetic flux (Glancy & Balaban, 2012; McCormack et al., 1990), may explain the increased flux in P42 muscles, we assessed mitochondrial calcium using Rhod-2 fluorescence (Fig.”
Method
SERCA1 expression enhances the metabolic efficiency of improved contractility in post-ischemic heart
O’Donnell, J. M., Pound, K. M., Xu, X., & Lewandowski, E. D. (2009) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2009.08.031 · Cited by 20
“The process is regulated by intramitochondrial calcium, pH [5,6], αKG availability, and redox state (NADH/NAD+) [15,37].”
Influential
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Mathematical model of compartmentalized energy transfer: Its use for analysis and interpretation of 31 P-NMR studies of isolated heart of creatine kinase deficient mice
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“of the respiration chain in the maintenance of cellular bioenergetics (59, 60).”
Background
Renal insufficiency induced by cisplatin in rats is ameliorated by cyclosporin A
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Background
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“Ca2+ in the mitochondrial matrix stimulates pyruvate, isocitrate and α-ketoglutarate dehydrogenase (McCormack et al., 1990), which reduce NAD to NADH in the citric acid cycle, as well as the F1F0-ATPase (Territo et al.”
Background
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“(5), but also influences neural signaling by modulating the amplitude and durations of cytoplasmic Ca transients (8,37).”
Background
Arginase II inhibition prevents interleukin-8 production through regulation of p38 MAPK phosphorylation activated by loss of mitochondrial membrane potential in nLDL-stimulated hAoSMCs
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Mathematical model of compartmentalized energy transfer: Its use for analysis and interpretation of 31P-NMR studies of isolated heart of creatine kinase deficient mice
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“In mammals, it is known that direct Xux of cytosolic Ca into mitochondria stimulates the rate of NADH production and ATP output by the allosteric activation of matrix dehydrogenases (McCormack et al. 1990), so that energy production is synchronized with the energy demands of Ca-activated processes in extramitochondria…”
Background
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“A previously unknown and perhaps more important role was indicated by the observations of Denton, McCormack, and coworkers (8), who found that the activity of pyruvate, isocitrate, and oxoglutarate dehydrogenases in permeabilized or homogenized mitochondria was enhanced by Ca2+.”
Background
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Leo, V. D., Gomes, T. M. B., & Vincent, A. E. (2023) · Biochemical Journal · doi:10.1042/bcj20220233 · Cited by 18
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“Inside mitochondria, calcium will have several effects including stimulation of mitochondrial NADH generation by the activation of some dehydrogenases (pyruvate dehydrogenase, isocitrate dehydrogenase and 2-oxoglutarate dehydrogenase) [14,15] and a regulatory effect on the mitochondrial ATP synthase [16].”
Background
Proton Modulation of Cardiac I Na: A Potential Arrhythmogenic Trigger
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“Such a lesser energy utilization, during MCU inhibition, may primarily occur due to nonacceleration of Ca2 +-dependent mitochondrial dehydrogenase enzymes (the pyruvate, a-ketoglutarate, and isocitrate dehydrogenases) during evoked neural activation (McCormack et al, 1990; Duchen, 2000).”
Background
3-Bromopyruvate inhibits calcium uptake by sarcoplasmic reticulum vesicles but not SERCA ATP hydrolysis activity
Messeder, D. J., Camacho-Pereira, J., & Galina, A. (2012) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2012.02.002 · Cited by 17
Intravenous lipid infusion results in myocardial lipid droplet accumulation combined with reduced myocardial performance in heparinized rabbits
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“The three major rate limiting enzymes of the citric acid cycle (isocitrate dehydrogenase, citrate synthase, ketoglutarate dehydrogenase) are all upregulated by Ca2+, thereafter mitochondrial Ca2+ uptake increases mitochondrial ATP production [38,39].”
Background
Cardiac Autoantibodies in Viral Myocarditis
Dörner, A., Kallwellis-Opara, A., Pauschinger, M., Kühl, U., & Schultheiß, H. (2005) · Heart Failure Clinics · doi:10.1016/j.hfc.2005.06.010 · Cited by 18
“[67].”
The use of the Ca2+‐sensitive intramitochondrial dehydrogenases and entrapped fura‐2 to study Sr2+ and Ba2+ transport across the inner membrane of mammalian mitochondria
McCormack, J. G., & Osbaldeston, N. J. (1990) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1990.tb19221.x · Cited by 17
Self-citation
Effects of insulin and guanosine 5′-[γ-thio]triphosphate on fatty acid synthesis and lipolysis within electropermeabilized fat-cells
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Self-citation
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“Calcium being an important driver for TCA cycle leading to mitochondrial oxygen consumption [49], this could explain drop in thrombin-induced spike in OCR in the presence of MLKL inhibitors.”
Background
Dietary amino acids promote glucagon-like hormone release to generate global calcium waves in adipose tissues in Drosophila
Ahmad, M., Wu, S., Luo, S., et al. (2025) · Nature Communications · doi:10.1038/s41467-024-55371-y · Cited by 16
“ICWs are complex tissue-level biological events that widely exist in multicellular organisms and impact many processes, e.g., muscle contraction 10,11 , gene expression 12,13 , cellular proliferation 14 , differentiation 15 , neuronal ﬁ ring and excitability 16 , and metabolism 17 .”
Comparative Microarray Analysis Identifies Commonalities in Neuronal Injury: Evidence for Oxidative Stress, Dysfunction of Calcium Signalling, and Inhibition of Autophagy–Lysosomal Pathway
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“Also, an increase of cytoplasmic calcium seems to be necessary for lysosome–lysosome fusion [117], lysosome–phagosome fusion [118], and lysosome-plasma membrane fusion [119].”
Background
Increased Histone Deacetylase Activity Involved in the Suppressed Invasion of Cancer Cells Survived from ALA-Mediated Photodynamic Treatment
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“by dysfunctional mitochondria [44,45].”
Interorganellar Membrane Microdomains: Dynamic Platforms in the Control of Calcium Signaling and Apoptosis
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“Once in the mitochondria, Ca acts as an important cofactor that activates and regulates Cadependent dehydrogenases of the Krebs cycle for maintenance of mitochondrial respiration and ATP production [29,30].”
Background
Pharynx mitochondrial [Ca2+] dynamics in live C. elegans worms during aging
Álvarez-Illera, P., García-Casas, P., Arias-del-Val, J., Fonteríz, R. I., Álvarez, J., & Montero, M. (2017) · Oncotarget · doi:10.18632/oncotarget.18600 · Cited by 16
“When cells are activated, the [Ca2+] rises first in the cytosol and then enters the mitochondria through the mitochondrial Ca2+ uniporter, activating several key dehydrogenases to boost substrate oxidation and ATP production [17-19].”
Background
Calcium Signalling: Mitofusins Promote Interorganellar Crosstalk
Parekh, A. B. (2009) · Current Biology · doi:10.1016/j.cub.2009.01.012 · Cited by 16
Mitochondrial protonophoric activity induced by a thyromimetic fatty acid analogue
Hermesh, O., Kalderon, B., Berman, B. P., & Bar‐Tana, J. (2000) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(00)00097-9 · Cited by 16
Redox regulation of endogenous substrate oxidation by cardiac mitochondria
Kôrge, P., & Weiss, J. N. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01292.2005 · Cited by 16
“Flickering would be stimulated by uptake of the contaminant Ca2 (30), which could explain the effect of EGTA (Fig.”
BackgroundInfluential
Chapter 10 Calcium flux measurements in apoptosis
McConkey, D. J., & Nutt, L. K. (2001) · Methods in cell biology · doi:10.1016/s0091-679x(01)66011-4 · Cited by 16
Enhancing effect of taurine on glucose response in UCP2-overexpressing beta cells
Lee, S. H., Hyun-Young, L., Kim, S.-Y., Lee, I., & Song, D. (2004) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2003.08.018 · Cited by 16
“It has been well known that a large amount of mitochondrial Ca concentration is needed to activate Ca-sensitive dehydrogenases, which are involved in the citric acid cycle for glucose oxidation [21].”
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Mitochondrial transporter responsiveness and metabolic flux homeostasis in postischemic hearts
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Authors: McCormack, J. G., Halestrap, A. P., & Denton, R. M.
Affiliations: University of Leeds (GB)
ORCID: Halestrap, A. P.
Venue: Physiological Reviews
Publisher: American Physiological Society
Published: 1990-04-01
Volume: 70
Issue: 2
Pages: 391-425
ISSN: 0031-9333 (ISSN-L)
1522-1210
DOI: 10.1152/physrev.1990.70.2.391
OpenAlex: W1935060748
Cited by: 1,398
References: 0
Citations by year: 2026: 18 · 2025: 21 · 2024: 16 · 2023: 33 · 2022: 26 · 2021: 44 · 2020: 40 · 2019: 39 · 2018: 36 · 2017: 40 · 2016: 47 · 2015: 37 · 2014: 53 · 2013: 63 · 2012: 68
FWCI: 10.57
Type: journal article
Language: en
Open access: closed
Locations: Physiological Reviews (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
Keywords: calcium ions, mitochondrial calcium, calcium signaling, mammalian mitochondria
MeSH terms: Animals, Calcium, Humans, Ions, Mammals, Mitochondria, Osmolar Concentration, Oxidoreductases, Oxygen Consumption, Pyrophosphatases

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Role of calcium ions in regulation of mammalian intramitochondrial metabolism

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