mitochondrial swelling


Summary: An increase in MITOCHONDRIAL VOLUME due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria.

Top Publications

  1. Kowaltowski A, Seetharaman S, Paucek P, Garlid K. Bioenergetic consequences of opening the ATP-sensitive K(+) channel of heart mitochondria. Am J Physiol Heart Circ Physiol. 2001;280:H649-57 pubmed
    ..Thus opening mitochondrial K(ATP) channels has little direct effect on respiration, membrane potential, or Ca(2+) uptake but has important effects on matrix and intermembrane space volumes. ..
  2. Hansson M, Persson T, Friberg H, Keep M, Rees A, Wieloch T, et al. Powerful cyclosporin inhibition of calcium-induced permeability transition in brain mitochondria. Brain Res. 2003;960:99-111 pubmed
    ..The importance of CsA causing a shift of the mitochondrial sensitivity to Ca(2+) in neurological disorders is discussed. ..
  3. Baines C, Kaiser R, Purcell N, Blair N, Osinska H, Hambleton M, et al. Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature. 2005;434:658-62 pubmed
    ..The mitochondrial permeability transition (mPT) leads to mitochondrial swelling, outer membrane rupture and the release of apoptotic mediators...
  4. Hansson M, Månsson R, Morota S, Uchino H, Kallur T, Sumi T, et al. Calcium-induced generation of reactive oxygen species in brain mitochondria is mediated by permeability transition. Free Radic Biol Med. 2008;45:284-94 pubmed publisher
    ..of calcium-induced ROS and their efficacy clearly paralleled their potency of inhibiting mPT-mediated mitochondrial swelling. We conclude that while intact respiring mitochondria possess powerful antioxidant capability, mPT induces ..
  5. Klein B, Wörndl K, Lütz Meindl U, Kerschbaum H. Perturbation of intracellular K(+) homeostasis with valinomycin promotes cell death by mitochondrial swelling and autophagic processes. Apoptosis. 2011;16:1101-17 pubmed publisher
    ..Valinomycin treatment induced mitochondrial swelling and minor nuclear changes in cell lines (BV-2, C6, HEK 293), and in primary mouse microglia and astrocytes...
  6. Krauskopf A, Eriksson O, Craigen W, Forte M, Bernardi P. Properties of the permeability transition in VDAC1(-/-) mitochondria. Biochim Biophys Acta. 2006;1757:590-5 pubmed
    ..The labeled protein could be separated from all VDAC isoforms. While these results do not allow to exclude that VDAC is part of the PTP, they suggest that VDAC is not the target for PTP inhibition by Ro 68-3400. ..
  7. Nakagawa T, Shimizu S, Watanabe T, Yamaguchi O, Otsu K, Yamagata H, et al. Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature. 2005;434:652-8 pubmed
    ..In addition, CypD-deficient mice showed a high level of resistance to ischaemia/reperfusion-induced cardiac injury. Our results indicate that the CypD-dependent mPT regulates some forms of necrotic death, but not apoptotic death. ..
  8. Wilson J, Bigelow C, Calkins D, Foster T. Light scattering from intact cells reports oxidative-stress-induced mitochondrial swelling. Biophys J. 2005;88:2929-38 pubmed
    ..J cm(-2) of 514 nm light led to pronounced changes in angularly resolved light scattering consistent with mitochondrial swelling. Electron microscopy of similarly treated EMT6 cell monolayers showed significant changes in mitochondrial ..
  9. Schinzel A, Takeuchi O, Huang Z, Fisher J, Zhou Z, Rubens J, et al. Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia. Proc Natl Acad Sci U S A. 2005;102:12005-10 pubmed

More Information


  1. Adembri C, Venturi L, Tani A, Chiarugi A, Gramigni E, Cozzi A, et al. Neuroprotective effects of propofol in models of cerebral ischemia: inhibition of mitochondrial swelling as a possible mechanism. Anesthesiology. 2006;104:80-9 pubmed
    ..mechanism of action, the authors then examined whether propofol could reduce Ca2+-induced rat brain mitochondrial swelling, an index of mitochondrial membrane permeability, as well as the mitochondrial swelling evoked by oxygen-..
  2. Shalbuyeva N, Brustovetsky T, Bolshakov A, Brustovetsky N. Calcium-dependent spontaneously reversible remodeling of brain mitochondria. J Biol Chem. 2006;281:37547-58 pubmed
    ..model suggests an involvement of the Ca(2+)-dependent transient K(+) influx into the matrix causing mitochondrial swelling followed by activation of the K(+)/H(+) exchanger leading to spontaneous mitochondrial contraction both in ..
  3. Kaasik A, Safiulina D, Choubey V, Kuum M, Zharkovsky A, Veksler V. Mitochondrial swelling impairs the transport of organelles in cerebellar granule neurons. J Biol Chem. 2007;282:32821-6 pubmed
    ..We propose that the size and morphology of the transported cargo is also relevant for seamless axonal transport and speculate that mitochondrial swelling could be one of the reasons for impaired organelle transport in neuronal processes.
  4. Belzacq Casagrande A, Martel C, Pertuiset C, Borgne Sanchez A, Jacotot E, Brenner C. Pharmacological screening and enzymatic assays for apoptosis. Front Biosci (Landmark Ed). 2009;14:3550-62 pubmed
    ..e. ANT, VDAC) and MMP. These assays should be useful tools to investigate mitochondrial apoptosis, decipher the implication of inner and outer membrane permeabilization and provide a multi-parametric approach for drug discovery. ..
  5. Salomão K, De Santana N, Molina M, de Castro S, Menna Barreto R. Trypanosoma cruzi mitochondrial swelling and membrane potential collapse as primary evidence of the mode of action of naphthoquinone analogues. BMC Microbiol. 2013;13:196 pubmed publisher
    ..The present study evaluated the activities of sixteen NQs derivatives on Trypanosoma cruzi...
  6. Gerencser A, Doczi J, Torocsik B, Bossy Wetzel E, Adam Vizi V. Mitochondrial swelling measurement in situ by optimized spatial filtering: astrocyte-neuron differences. Biophys J. 2008;95:2583-98 pubmed publisher
    b>Mitochondrial swelling is a hallmark of mitochondrial dysfunction, and is an indicator of the opening of the mitochondrial permeability transition pore...
  7. Månsson R, Hansson M, Morota S, Uchino H, Ekdahl C, Elmér E. Re-evaluation of mitochondrial permeability transition as a primary neuroprotective target of minocycline. Neurobiol Dis. 2007;25:198-205 pubmed
    ..Minocycline, at high dosage, was found to prevent calcium-induced mitochondrial swelling under energized conditions similarly to the mPT inhibitor cyclosporin A (CsA) in rodent mitochondria ..
  8. Guo H, Wang F, Yu K, Chen J, Bai D, Chen K, et al. Novel cyclophilin D inhibitors derived from quinoxaline exhibit highly inhibitory activity against rat mitochondrial swelling and Ca2+ uptake/ release. Acta Pharmacol Sin. 2005;26:1201-11 pubmed
    ..Compounds GW2, 5, 6, and 7 had high inhibition activities against Ca(2+)-dependent rat liver mitochondrial swelling and Ca(2+) uptake/release. Compound GW5 had binding selectivity for CypD over CypA...
  9. Wiedemann N, Truscott K, Pfannschmidt S, Guiard B, Meisinger C, Pfanner N. Biogenesis of the protein import channel Tom40 of the mitochondrial outer membrane: intermembrane space components are involved in an early stage of the assembly pathway. J Biol Chem. 2004;279:18188-94 pubmed
    ..We propose that the biogenesis pathway of beta-barrel proteins of the outer mitochondrial membrane not only requires TOM and SAM components, but also involves components of the intermembrane space. ..
  10. Costa A, Quinlan C, Andrukhiv A, West I, Jaburek M, Garlid K. The direct physiological effects of mitoK(ATP) opening on heart mitochondria. Am J Physiol Heart Circ Physiol. 2006;290:H406-15 pubmed
    ..These results provide decisive support for the hypothesis that mitochondria contain an ATP-sensitive K+ channel and establish the physiological consequences of mitoK(ATP) opening for mitochondria. ..
  11. Domoki F, Bari F, Nagy K, Busija D, Siklos L. Diazoxide prevents mitochondrial swelling and Ca2+ accumulation in CA1 pyramidal cells after cerebral ischemia in newborn pigs. Brain Res. 2004;1019:97-104 pubmed
    ..p<0.05) at 10-15-min reperfusion time. In this interval, pretreatment with DIAZ virtually abolished mitochondrial swelling (6.88+/-0.49%) and Ca(2+) accumulation (5.15+/-0.82%) evoked by I/R...
  12. Seye C, Knaapen M, Daret D, Desgranges C, Herman A, Kockx M, et al. 7-Ketocholesterol induces reversible cytochrome c release in smooth muscle cells in absence of mitochondrial swelling. Cardiovasc Res. 2004;64:144-53 pubmed
    ..The reversibility of these events suggests that the apoptotic cascade could be arrested before a point of no return. ..
  13. Sesso A, Belizario J, Marques M, Higuchi M, Schumacher R, Colquhoun A, et al. Mitochondrial swelling and incipient outer membrane rupture in preapoptotic and apoptotic cells. Anat Rec (Hoboken). 2012;295:1647-59 pubmed publisher
    ..No channel within the outer membrane can expose to the cytoplasm a permeable inner membrane, because it would serve as a conduit for local herniation of the mitochondrial matrix...
  14. Morota S, Manolopoulos T, Eyjolfsson A, Kimblad P, Wierup P, Metzsch C, et al. Functional and pharmacological characteristics of permeability transition in isolated human heart mitochondria. PLoS ONE. 2013;8:e67747 pubmed publisher
    ..The findings support that inhibition of mPT may be a relevant pharmacological target in human cardiac disease and may underlie the beneficial effect of cyclosporin A in reperfusion injury. ..
  15. Halestrap A. Biochemistry: a pore way to die. Nature. 2005;434:578-9 pubmed
  16. Skulachev V. Why are mitochondria involved in apoptosis? Permeability transition pores and apoptosis as selective mechanisms to eliminate superoxide-producing mitochondria and cell. FEBS Lett. 1996;397:7-10 pubmed
    ..Another result of the long-lived pores is mitochondrial swelling. This disrupts the outer mitochondrial membrane and releases the apoptosis-inducing protein...
  17. Petit P, Goubern M, Diolez P, Susin S, Zamzami N, Kroemer G. Disruption of the outer mitochondrial membrane as a result of large amplitude swelling: the impact of irreversible permeability transition. FEBS Lett. 1998;426:111-6 pubmed
    ..Moreover, they confirm the hypothesis formulated by Skulachev [FEBS Lett. 397 (1996) 7-10 and Q. Rev. Biophys. 29 (1996) 169-2021 linking permeability transition to activation of the apoptogenic catabolic enzymes. ..
  18. Das M, Parker J, Halestrap A. Matrix volume measurements challenge the existence of diazoxide/glibencamide-sensitive KATP channels in rat mitochondria. J Physiol. 2003;547:893-902 pubmed
    ..2 nM), produced a 10-20 % increase in matrix volume that was readily detectable by both techniques. Our data argue against the existence of a sulphonylurea-inhibitable mitoKATP channel. ..
  19. Bernardi P, Scorrano L, Colonna R, Petronilli V, Di Lisa F. Mitochondria and cell death. Mechanistic aspects and methodological issues. Eur J Biochem. 1999;264:687-701 pubmed
  20. Kobayashi T, Kuroda S, Tada M, Houkin K, Iwasaki Y, Abe H. Calcium-induced mitochondrial swelling and cytochrome c release in the brain: its biochemical characteristics and implication in ischemic neuronal injury. Brain Res. 2003;960:62-70 pubmed
    The objective of the present study was to determine the biochemical characteristics of Ca(2+)-induced mitochondrial swelling (mitochondrial permeability transition; mPT) and cytochrome c release in the brain, and to clarify its role in ..
  21. Wigdal S, Kirkland R, Franklin J, Haak Frendscho M. Cytochrome c release precedes mitochondrial membrane potential loss in cerebellar granule neuron apoptosis: lack of mitochondrial swelling. J Neurochem. 2002;82:1029-38 pubmed
    ..These findings suggest that mitochondrial permeability transition pore is not involved in Cyt c release from mitochondria during the apoptotic death of cerebellar granule neurons. ..
  22. Casley C, Land J, Sharpe M, Clark J, Duchen M, Canevari L. Beta-amyloid fragment 25-35 causes mitochondrial dysfunction in primary cortical neurons. Neurobiol Dis. 2002;10:258-67 pubmed
    ..decrease in the specific activity of mitochondrial enzymes per milligram of cellular protein, induced mitochondrial swelling, and decreased total mitochondrial number...
  23. del Rio G, Castro Obregon S, Rao R, Ellerby H, Bredesen D. APAP, a sequence-pattern recognition approach identifies substance P as a potential apoptotic peptide. FEBS Lett. 2001;494:213-9 pubmed
    ..Among other peptides, substance P was identified as a PAP and subsequently demonstrated to be a pro-apoptotic peptide experimentally. APAP thus provides a method to detect and ultimately improve pro-apoptotic peptides for chemotherapy. ..
  24. Gao W, Pu Y, Luo K, Chang D. Temporal relationship between cytochrome c release and mitochondrial swelling during UV-induced apoptosis in living HeLa cells. J Cell Sci. 2001;114:2855-62 pubmed
    ..This finding strongly suggests that cytochrome c release in apoptosis was not caused by mitochondrial swelling. This conclusion was further supported in two separated experiments using an immunostaining method and ..
  25. Kristian T, Bernardi P, Siesjo B. Acidosis promotes the permeability transition in energized mitochondria: implications for reperfusion injury. J Neurotrauma. 2001;18:1059-74 pubmed
  26. Moreira P, Santos M, Moreno A, Rego A, Oliveira C. Effect of amyloid beta-peptide on permeability transition pore: a comparative study. J Neurosci Res. 2002;69:257-67 pubmed
    ..demonstrated a higher capacity to accumulate Ca(2+) before the Delta Psi m drop and a slight increase of mitochondrial swelling compared with liver mitochondria...
  27. Halestrap A, Davidson A. Inhibition of Ca2(+)-induced large-amplitude swelling of liver and heart mitochondria by cyclosporin is probably caused by the inhibitor binding to mitochondrial-matrix peptidyl-prolyl cis-trans isomerase and preventing it interacting with the adenin. Biochem J. 1990;268:153-60 pubmed
    ..J. 268, 147-152]. 6. The physiological and pathological implications of the model are discussed in relation to reperfusion injury and cyclosporin toxicity. ..
  28. Lu X, Chen W. Effect of 3, 4-dihydroxyacetophenone on Na+, K+ -ATPase activity of injured mitochondria and the oxygen consumption of brain cells of rat. Yao Xue Xue Bao. 2005;40:13-6 pubmed
    ..alpha-DHAP can protect the structure and the function of brain mitochondria and cells by scavenging the free radical and resisting the reaction of lipid peroxidation. ..
  29. Sorrentino G, Comel A, Del Sal G. p53 orchestrates calcium signaling in vivo. Cell Cycle. 2015;14:1343-4 pubmed publisher
  30. Layton B, Sastry A, Lastoskie C, Philbert M, Miller T, Sullivan K, et al. In situ imaging of mitochondrial outer-membrane pores using atomic force microscopy. Biotechniques. 2004;37:564-70, 572-3 pubmed
    ..We have also begun to correlate 3-D surface features of mitochondria dotted with open membrane pores with features previously viewed with electron microscopy (EM) of fixed sections. ..
  31. Serkov I, Shevtsova E, Dubova L, Kireeva E, Vishnevskaya E, Gretskaya N, et al. Interaction of docosahexaenoic acid derivatives with mitochondria. Dokl Biol Sci. 2007;414:187-9 pubmed
  32. Chen T, Wang X, Sun L, Wang L, Xing D, Mok M. Taxol induces caspase-independent cytoplasmic vacuolization and cell death through endoplasmic reticulum (ER) swelling in ASTC-a-1 cells. Cancer Lett. 2008;270:164-72 pubmed publisher
    ..In conclusion, we found for the first time that taxol induces a paraptosis-like PCD in the ASTC-a-1 cells by cytoplasm vacuolization due to the swelling of both ER and mitochondria without activating the caspase enzymes. ..
  33. Azarashvili T, Krestinina O, Galvita A, Grachev D, Baburina Y, Stricker R, et al. Ca2+-dependent permeability transition regulation in rat brain mitochondria by 2',3'-cyclic nucleotides and 2',3'-cyclic nucleotide 3'-phosphodiesterase. Am J Physiol Cell Physiol. 2009;296:C1428-39 pubmed publisher
    ..This Ca(2+) release under threshold Ca(2+) load correlated with membrane potential dissipation and mitochondrial swelling. The effects of 2',3'-cyclic nucleotides were suppressed by cyclosporin A, a potent inhibitor of ..
  34. Drahota Z, Milerova M, Endlicher R, Rychtrmoc D, Cervinkova Z, Ost ádal B. Developmental changes of the sensitivity of cardiac and liver mitochondrial permeability transition pore to calcium load and oxidative stress. Physiol Res. 2012;61 Suppl 1:S165-72 pubmed
    ..cardiac mitochondria were more resistant also to the peroxide activating effect on calcium-induced mitochondrial swelling. These data thus indicate that the MPTP of heart mitochondria is better protected against damaging effects ..
  35. da Silva M, da Rosa E, de Carvalho N, Dobrachinski F, da Rocha J, Mauriz J, et al. Acute brain damage induced by acetaminophen in mice: effect of diphenyl diselenide on oxidative stress and mitochondrial dysfunction. Neurotox Res. 2012;21:334-44 pubmed publisher
    ..brain mitochondria were examined to quantify mitochondrial transmembrane's electrical potential and mitochondrial swelling and to estimate reactive oxygen species (ROS) production...
  36. Imaizumi N, Aniya Y. The role of a membrane-bound glutathione transferase in the peroxynitrite-induced mitochondrial permeability transition pore: formation of a disulfide-linked protein complex. Arch Biochem Biophys. 2011;516:160-72 pubmed publisher
  37. Valdameri G, Herrerias T, Carnieri E, Cadena S, Martinez G, Rocha M. Importance of the core structure of flavones in promoting inhibition of the mitochondrial respiratory chain. Chem Biol Interact. 2010;188:52-8 pubmed publisher
    ..Flavone at certain doses (75-200 micromol L(-1)) reduced mitochondrial swelling in the presence of valinomycin and KNO(3), suggesting that flavone could induce changes in mitochondrial ..
  38. McMartin K, Wallace K. Calcium oxalate monohydrate, a metabolite of ethylene glycol, is toxic for rat renal mitochondrial function. Toxicol Sci. 2005;84:195-200 pubmed
    ..COM, from 0.01-0.05 mM also dose-dependently increased mitochondrial swelling, which was completely blocked by cyclosporin A...
  39. Plin C, Haddad P, Tillement J, Elimadi A, Morin D. Protection by cyclosporin A of mitochondrial and cellular functions during a cold preservation-warm reperfusion of rat liver. Eur J Pharmacol. 2004;495:111-8 pubmed
    ..CPWR induced damages on the mitochondrial respiratory chain, leading to mitochondrial swelling. The consequences are the loss of ATP energetic charge, the initiation of apoptosis through cytochrome c ..
  40. Park J, Jang S, Shin Y, Koh H, Suh D, Shinji T, et al. Mitochondrial swelling and microtubule depolymerization are associated with energy depletion in axon degeneration. Neuroscience. 2013;238:258-69 pubmed publisher intimately related to axonal degeneration following nerve injury, the molecular mechanisms of mitochondrial swelling and its mechanistic relation to axonal degeneration are largely unknown...
  41. Ventura F, Ruiter J, Ijlst L, de Almeida I, Wanders R. Differential inhibitory effect of long-chain acyl-CoA esters on succinate and glutamate transport into rat liver mitochondria and its possible implications for long-chain fatty acid oxidation defects. Mol Genet Metab. 2005;86:344-52 pubmed
    ..This conclusion was substantiated by mitochondrial swelling studies, which showed inhibition of succinate transport by the different CoA esters whereas no effect was ..
  42. García N, Martínez Abundis E, Pavón N, Chávez E. Sodium inhibits permeability transition by decreasing potassium matrix content in rat kidney mitochondria. Comp Biochem Physiol B Biochem Mol Biol. 2006;144:442-50 pubmed
    ..It is concluded that the protection provided by Na+ was accomplished by inducing matrix K+ depletion, which, in turn, diminished the free fraction of matrix Ca2+. ..
  43. Queiroga C, Almeida A, Alves P, Brenner C, Vieira H. Carbon monoxide prevents hepatic mitochondrial membrane permeabilization. BMC Cell Biol. 2011;12:10 pubmed publisher
    ..Direct and indirect approaches were used to evaluate MMP inhibition by CO: mitochondrial swelling, mitochondrial depolarization and inner membrane permeabilization...
  44. Pires A, Noleto G, Echevarria A, Dos Reis C, Rocha M, Carnieri E, et al. Interaction of 1,3,4-thiadiazolium mesoionic derivatives with mitochondrial membrane and scavenging activity: Involvement of their effects on mitochondrial energy-linked functions. Chem Biol Interact. 2011;189:17-25 pubmed publisher
    ..b>Mitochondrial swelling in the absence of substrate was inhibited by all derivatives; however, the fluorine derivatives were most ..
  45. de Arriba G, de Hornedo J, Rubio S, Fernández M, Martínez S, Camarero M, et al. Vitamin E protects against the mitochondrial damage caused by cyclosporin A in LLC-PK1 cells. Toxicol Appl Pharmacol. 2009;239:241-50 pubmed publisher
    ..These features are related to apoptosis and can explain the cellular damage that CsA induces. As Vit E inhibited these effects, our results suggest that they were mediated by an increase in ROS production by mitochondria. ..
  46. Baines C, Kaiser R, Sheiko T, Craigen W, Molkentin J. Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nat Cell Biol. 2007;9:550-5 pubmed
    ..These results indicate that Vdacs are dispensable for both MPT and Bcl-2 family member-driven cell death. ..
  47. Mironova G, Shigaeva M, Belosludtseva N, Gritsenko E, Belosludtsev K, Germanova E, et al. Effect of several flavonoid-containing plant preparations on activity of mitochondrial ATP-dependent potassium channel. Bull Exp Biol Med. 2008;146:229-33 pubmed
    ..Under in vivo conditions, the antihypoxic effect of Extralife was partially abolished by mitochondrial ATP-dependent potassium channel inhibitor 5-hydroxydecanoate. ..
  48. La Salete R, Oliveira M, Palmeira C, Almeida J, Peixoto F. Mitochondria a key role in microcystin-LR kidney intoxication. J Appl Toxicol. 2008;28:55-62 pubmed
    ..with ruthenium red resulted in mitochondrial permeability transition pore (MPTP) opening, as evidenced by mitochondrial swelling in isosmotic sucrose medium...
  49. Velosa A, Baader W, Stevani C, Mano C, Bechara E. 1,3-diene probes for detection of triplet carbonyls in biological systems. Chem Res Toxicol. 2007;20:1162-9 pubmed
    ..Experiments with model systems used widely to study lipid peroxidation showed that sorbate can inhibit mitochondrial swelling induced by enzymically formed triplet benzophenone and quench the chemiluminescence of microsome ..
  50. Lizana L, Bauer B, Orwar O. Controlling the rates of biochemical reactions and signaling networks by shape and volume changes. Proc Natl Acad Sci U S A. 2008;105:4099-104 pubmed publisher
  51. Wojtovich A, Williams D, Karcz M, Lopes C, Gray D, NEHRKE K, et al. A novel mitochondrial K(ATP) channel assay. Circ Res. 2010;106:1190-6 pubmed publisher
    ..2 than the K(IR)6.1 isoform. The effect of fluoxetine on mK(ATP)-dependent cardioprotection has implications for the growing use of antidepressants in patients who may benefit from preconditioning. ..
  52. Sun Q, Chen T, Wang X, Wei X. Taxol induces paraptosis independent of both protein synthesis and MAPK pathway. J Cell Physiol. 2010;222:421-32 pubmed publisher
    ..These results suggest that high concentration of taxol activates an alternative paraptotic cell death pathway. ..