Chapter 28
Imaging Mitochondrial Membrane Potential and Inner Membrane Permeability
Anna-Liisa Nieminen,
Venkat K. Ramshesh,
John J. Lemasters,
Anna-Liisa Nieminen
Center for Cell Death, Injury & Regeneration, Medical University of South Carolina, Charleston, SC, USA
Department of Drug Discovery & Biomedical Sciences, Medical University of South Carolina, Charleston, SC, USA
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russian Federation
Search for more papers by this authorVenkat K. Ramshesh
Center for Cell Death, Injury & Regeneration, Medical University of South Carolina, Charleston, SC, USA
Department of Drug Discovery & Biomedical Sciences, Medical University of South Carolina, Charleston, SC, USA
GE Healthcare, Quincy, MA, USA
Search for more papers by this authorJohn J. Lemasters
Center for Cell Death, Injury & Regeneration, Medical University of South Carolina, Charleston, SC, USA
Department of Drug Discovery & Biomedical Sciences, Medical University of South Carolina, Charleston, SC, USA
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russian Federation
Department of Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, SC, USA
Search for more papers by this authorAnna-Liisa Nieminen,
Venkat K. Ramshesh,
John J. Lemasters,
Anna-Liisa Nieminen
Center for Cell Death, Injury & Regeneration, Medical University of South Carolina, Charleston, SC, USA
Department of Drug Discovery & Biomedical Sciences, Medical University of South Carolina, Charleston, SC, USA
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russian Federation
Search for more papers by this authorVenkat K. Ramshesh
Center for Cell Death, Injury & Regeneration, Medical University of South Carolina, Charleston, SC, USA
Department of Drug Discovery & Biomedical Sciences, Medical University of South Carolina, Charleston, SC, USA
GE Healthcare, Quincy, MA, USA
Search for more papers by this authorJohn J. Lemasters
Center for Cell Death, Injury & Regeneration, Medical University of South Carolina, Charleston, SC, USA
Department of Drug Discovery & Biomedical Sciences, Medical University of South Carolina, Charleston, SC, USA
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russian Federation
Department of Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, SC, USA
Search for more papers by this authorBook Editor(s):Yvonne Will PhD, ATS Fellow,
James A. Dykens,
Yvonne Will PhD, ATS Fellow
Pfizer Drug Safety R&D, Groton, CT, USA
Search for more papers by this authorFirst published: 23 February 2018
Summary
A proton motive force generated by respiratory chain components in the mitochondrial inner membrane drives mitochondrial adenosine triphosphate (ATP) production. Isolation of mitochondria from brain tissue is more problematic because of the intrinsic cellular heterogeneity of the nervous system. Mitochondrial fractions from the brain are typically contaminated with synaptosomes. In the mitochondrial permeability transition (MPT), opening of nonselective, highly conductive permeability transition (PT) pores causes the inner membrane of mitochondria to become permeable to molecules of up to 1500 Da, which leads to mitochondrial depolarization. The molecular composition of PT pores remains uncertain. In one model, PT pores form from the adenine nucleotide translocator (ANT) in the inner membrane, the voltage- dependent anion channel (VDAC) in the outer membrane, and cyclophilin D (CypD), a CsA binding protein from the matrix. In another model, PT pores form from damaged misfolded membrane proteins that aggregate at hydrophilic surfaces facing the bilayer to create aqueous transmembrane channels.
References
- Akerman, K. E. and M. K. Wikstrom (1976). “Safranine as a probe of the mitochondrial membrane potential.” FEBS Lett 68(2): 191–197.
- Baines, C. P., R. A. Kaiser, T. Sheiko, W. J. Craigen and J. D. Molkentin (2007). “Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death.” Nat Cell Biol 9(5): 550–555.
- Basso, E., L. Fante, J. Fowlkes, V. Petronilli, M. A. Forte and P. Bernardi (2005). “Properties of the permeability transition pore in mitochondria devoid of Cyclophilin D.” J Biol Chem 280(19): 18558–18561.
-
Battino, M., A. Gorini, R. F. Villa, M. L. Genova, C. Bovina, S. Sassi, G. P. Littarru and G. Lenaz (1995). “Coenzyme Q content in synaptic and non-synaptic mitochondria from different brain regions in the ageing rat.” Mech Ageing Dev
78(3): 173–187.
10.1016/0047-6374(94)01535-T Google Scholar
- Bernardi, P., A. Rasola, M. Forte and G. Lippe (2015). “The mitochondrial permeability transition pore: channel formation by F-ATP synthase, integration in signal transduction, and role in pathophysiology.” Physiol Rev 95(4): 1111–1155.
- Biasutto, L., M. Azzolini, I. Szabo and M. Zoratti (2016). “The mitochondrial permeability transition pore in AD 2016: an update.” Biochim Biophys Acta 1863(10): 2515–2530.
- Blattner, J. R., L. He and J. J. Lemasters (2001). “Screening assays for the mitochondrial permeability transition using a fluorescence multiwell plate reader.” Anal Biochem 295(2): 220–226.
- Brouillet, E., C. Jacquard, N. Bizat and D. Blum (2005). “3-Nitropropionic acid: a mitochondrial toxin to uncover physiopathological mechanisms underlying striatal degeneration in Huntington's disease.” J Neurochem 95(6): 1521–1540.
-
Brustovetsky, N., R. Jemmerson and J. M. Dubinsky (2002). “Calcium-induced cytochrome c release from rat brain mitochondria is altered by digitonin.” Neurosci Lett
332(2): 91–94.
10.1016/S0304-3940(02)00948-5 Google Scholar
- Chacon, E., J. M. Reece, A. L. Nieminen, G. Zahrebelski, B. Herman and J. J. Lemasters (1994). “Distribution of electrical potential, pH, free Ca2+, and volume inside cultured adult rabbit cardiac myocytes during chemical hypoxia: a multiparameter digitized confocal microscopic study.” Biophys J 66(4): 942–952.
- Divakaruni, A. S., G. W. Rogers and A. N. Murphy (2014). “Measuring mitochondrial function in permeabilized cells using the seahorse XF analyzer or a clark-type oxygen electrode.” Curr Protoc Toxicol 60: 25.22.2.1–25.22.2.16.
- Ehrenberg, B., V. Montana, M. D. Wei, J. P. Wuskell and L. M. Loew (1988). “Membrane potential can be determined in individual cells from the Nernstian distribution of cationic dyes.” Biophys J 53: 785–794.
- Elmore, S. P., T. Qian, S. F. Grissom and J. J. Lemasters (2001). “The mitochondrial permeability transition initiates autophagy in rat hepatocytes.” FASEB J 15(12): 2286–2287.
- Emaus, R. K., R. Grunwald and J. J. Lemasters (1986). “Rhodamine 123 as a probe of transmembrane potential in isolated rat-liver mitochondria: spectral and metabolic properties.” Biochim Biophys Acta 850(3): 436–448.
- Epsztejn, S., O. Kakhlon, H. Glickstein, W. Breuer and I. Cabantchik (1997). “Fluorescence analysis of the labile iron pool of mammalian cells.” Anal Biochem 248(1): 31–40.
- Fiskum, G., S. W. Craig, G. L. Decker and A. L. Lehninger (1980). “The cytoskeleton of digitonin-treated rat hepatocytes.” Proc Natl Acad Sci U S A 77(6): 3430–3434.
- Gillan, L., G. Evans and W. M. Maxwell (2005). “Flow cytometric evaluation of sperm parameters in relation to fertility potential.” Theriogenology 63(2): 445–457.
- Glancy, B., L. M. Hartnell, D. Malide, Z. X. Yu, C. A. Combs, P. S. Connelly, S. Subramaniam and R. S. Balaban (2015). “Mitochondrial reticulum for cellular energy distribution in muscle.” Nature 523(7562): 617–620.
- Halestrap, A. P. and A. P. Richardson (2015). “The mitochondrial permeability transition: a current perspective on its identity and role in ischaemia/reperfusion injury.” J Mol Cell Cardiol 78: 129–141.
- He, L. and J. J. Lemasters (2002). “Regulated and unregulated mitochondrial permeability transition pores: a new paradigm of pore structure and function?” FEBS Lett 512(1–3): 1–7.
- Heiskanen, K. M., M. B. Bhat, H. W. Wang, J. Ma and A. L. Nieminen (1999). “Mitochondrial depolarization accompanies cytochrome c release during apoptosis in PC6 cells.” J Biol Chem 274(9): 5654–5658.
- Hunter, D. R., R. A. Haworth and J. H. Southard (1976). “Relationship between configuration, function, and permeability in calcium-treated mitochondria.” J Biol Chem 251: 5069–5077.
-
Hurst, S., J. Hoek and S. S. Sheu (2017). “Mitochondrial Ca2+ and regulation of the permeability transition pore.” J Bioenerg Biomembr
49(1): 27–47.
10.1007/s10863-016-9672-x Google Scholar
- Johnson, L. V., M. L. Walsh and L. B. Chen (1980). “Localization of mitochondria in living cells with rhodamine 123.” Proc Natl Acad Sci USA 77: 990–994.
- Johnson, L. V., M. L. Walsh, B. J. Bockus and L. B. Chen (1981). “Monitoring of relative mitochondrial membrane potential in living cells by fluorescence microscopy.” J Cell Biol 88: 526–535.
- Jonas, E. A., G. A. Porter Jr., G. Beutner, N. Mnatsakanyan and K. N. Alavian (2015). “Cell death disguised: the mitochondrial permeability transition pore as the c-subunit of the F(1)F(O) ATP synthase.” Pharmacol Res 99: 382–392.
- Kim, J. S., Y. Jin and J. J. Lemasters (2006). “Reactive oxygen species, but not Ca2+ overloading, trigger pH- and mitochondrial permeability transition-dependent death of adult rat myocytes after ischemia-reperfusion.” Am J Physiol Heart Circ Physiol 290(5): H2024–H2034.
- Klar, T. A., S. Jakobs, M. Dyba, A. Egner and S. W. Hell (2000). “Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission.” Proc Natl Acad Sci U S A 97(15): 8206–8210.
- Kokoszka, J. E., K. G. Waymire, S. E. Levy, J. E. Sligh, J. Cai, D. P. Jones, G. R. MacGregor and D. C. Wallace (2004). “The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore.” Nature 427(6973): 461–465.
-
Kon, K., J. S. Kim, A. Uchiyama, H. Jaeschke and J. J. Lemasters (2010). “Lysosomal iron mobilization and induction of the mitochondrial permeability transition in acetaminophen-induced toxicity to mouse hepatocytes.” Toxicol Sci
117(1): 101–108.
10.1093/toxsci/kfq175 Google Scholar
- Lam, M., N. L. Oleinick and A. L. Nieminen (2001). “Photodynamic therapy-induced apoptosis in epidermoid carcinoma cells. Reactive oxygen species and mitochondrial inner membrane permeabilization.” J Biol Chem 276(50): 47379–47386.
-
Lemasters, J. J. (2013). Hepatotoxicity due to mitochondrial injury. Drug-Induced Liver Disease. N. Kaplowitz and L. D. DeLeve. Amsterdam, Elsevier. 3rd edn., pp. 85–100.
10.1016/B978-0-12-387817-5.00005-4 Google Scholar
- Lemasters, J. J., J. DiGuiseppi, A. L. Nieminen and B. Herman (1987). “Blebbing, free Ca2+ and mitochondrial membrane potential preceding cell death in hepatocytes.” Nature 325(6099): 78–81.
- Lemasters, J. J. and C. R. Hackenbrock (1980). “The energized state of rat liver mitochondria. ATP equivalence, uncoupler sensitivity, and decay kinetics.” J Biol Chem 255: 5674–5680.
- Lemasters, J. J., T. P. Theruvath, Z. Zhong and A. L. Nieminen (2009). “Mitochondrial calcium and the permeability transition in cell death.” Biochim Biophys Acta 1787(11): 1395–1401.
-
Macho, A., D. Decaudin, M. Castedo, T. Hirsch, S. A. Susin, N. Zamzami and G. Kroemer (1996). “Chloromethyl-X-Rosamine is an aldehyde-fixable potential-sensitive fluorochrome for the detection of early apoptosis.” Cytometry
25(4): 333–340.
10.1002/(SICI)1097-0320(19961201)25:4<333::AID-CYTO4>3.0.CO;2-E CAS PubMed Web of Science® Google Scholar
-
Neupane, B., F. S. Ligler and G. Wang (2014). “Review of recent developments in stimulated emission depletion microscopy: applications on cell imaging.” J Biomed Opt
19(8): 080901.
10.1117/1.JBO.19.8.080901 Google Scholar
-
Nicholls, D. G. (2006). “Simultaneous monitoring of ionophore- and inhibitor-mediated plasma and mitochondrial membrane potential changes in cultured neurons.” J Biol Chem
281(21): 14864–14874.
10.1074/jbc.M510916200 Google Scholar
- Nicholls, D. G. (2012). “Fluorescence measurement of mitochondrial membrane potential changes in cultured cells.” Methods Mol Biol 810: 119–133.
-
Nicholls, D. G. and S. J. Ferguson (2013). Bioenergetics, 4th edn.
London, Elsevier.
10.1016/B978-0-12-388425-1.00009-9 Google Scholar
- Nieminen, A. L., G. J. Gores, T. L. Dawson, B. Herman and J. J. Lemasters (1990). “Toxic injury from mercuric chloride in rat hepatocytes.” J Biol Chem 265(4): 2399–2408.
- Nieminen, A. L., A. K. Saylor, S. A. Tesfai, B. Herman and J. J. Lemasters (1995). “Contribution of the mitochondrial permeability transition to lethal injury after exposure of hepatocytes to t-butylhydroperoxide.” Biochem J 307(Pt 1): 99–106.
- Ong, S. B., P. Samangouei, S. B. Kalkhoran and D. J. Hausenloy (2015). “The mitochondrial permeability transition pore and its role in myocardial ischemia reperfusion injury.” J Mol Cell Cardiol 78: 23–34.
-
Panov, A., S. Dikalov, N. Shalbuyeva, G. Taylor, T. Sherer and J. T. Greenamyre (2005). “Rotenone model of Parkinson disease: multiple brain mitochondria dysfunctions after short term systemic rotenone intoxication.” J Biol Chem
280(51): 42026–42035.
10.1074/jbc.M508628200 Google Scholar
- Petronilli, V., G. Miotto, M. Canton, M. Brini, R. Colonna, P. Bernardi and F. Di Lisa (1999). “Transient and long-lasting openings of the mitochondrial permeability transition pore can be monitored directly in intact cells by changes in mitochondrial calcein fluorescence.” Biophys J 76(2): 725–734.
-
Readnower, R. D., J. D. Pandya, M. L. McEwen, J. R. Pauly, J. E. Springer and P. G. Sullivan (2011). “Post-injury administration of the mitochondrial permeability transition pore inhibitor, NIM811, is neuroprotective and improves cognition after traumatic brain injury in rats.” J Neurotrauma
28(9): 1845–1853.
10.1089/neu.2011.1755 Google Scholar
- Reers, M., T. W. Smith and L. B. Chen (1991). “J-aggregate formation of a carbocyanine as a quantitative fluorescent indicator of membrane potential.” Biochemistry 30(18): 4480–4486.
- Reers, M., S. T. Smiley, C. Mottola-Hartshorn, A. Chen, M. Lin and L. B. Chen (1995). “Mitochondrial membrane potential monitored by JC-1 dye.” Methods Enzymol 260: 406–417.
-
Rottenberg, H. and S. Wu (1997). “Mitochondrial dysfunction in lymphocytes from old mice: enhanced activation of the permeability transition.” Biochem Biophys Res Commun
240(1): 68–74.
10.1006/bbrc.1997.7605 Google Scholar
-
Rottenberg, H. and S. Wu (1998). “Quantitative assay by flow cytometry of the mitochondrial membrane potential in intact cells.” Biochim Biophys Acta
1404(3): 393–404.
10.1016/S0167-4889(98)00088-3 Google Scholar
- Scaduto, R. C., Jr. and L. W. Grotyohann (1999). “Measurement of mitochondrial membrane potential using fluorescent rhodamine derivatives.” Biophys J 76(1 Pt 1): 469–477.
-
Scanlon, J. M. and I. J. Reynolds (1998). “Effects of oxidants and glutamate receptor activation on mitochondrial membrane potential in rat forebrain neurons.” J Neurochem
71(6): 2392–2400.
10.1046/j.1471-4159.1998.71062392.x Google Scholar
- Schneider, W. C. (1948). Intracellular distribution of enzymes: III. The oxidation of octanoic acid by rat liver fractions. J Biol Chem 176: 259–266.
- Shanmughapriya, S., S. Rajan, N. E. Hoffman, A. M. Higgins, D. Tomar, N. Nemani, K. J. Hines, D. J. Smith, A. Eguchi, S. Vallem, F. Shaikh, M. Cheung, N. J. Leonard, R. S. Stolakis, M. P. Wolfers, J. Ibetti, J. K. Chuprun, N. R. Jog, S. R. Houser, W. J. Koch, J. W. Elrod and M. Madesh (2015). “SPG7 is an essential and conserved component of the mitochondrial permeability transition pore.” Mol Cell 60(1): 47–62.
- Sims, N. R. and M. F. Anderson (2008). “Isolation of mitochondria from rat brain using Percoll density gradient centrifugation.” Nat Protoc 3(7): 1228–1239.
-
Trollinger, D. R., W. E. Cascio and J. J. Lemasters (1997). “Selective loading of Rhod 2 into mitochondria shows mitochondrial Ca2+ transients during the contractile cycle in adult rabbit cardiac myocytes.” Biochem Biophys Res Commun
236(3): 738–742.
10.1006/bbrc.1997.7042 Google Scholar
-
Tunez, I., I. Tasset, V. Perez-De La Cruz and A. Santamaria (2010). “3-Nitropropionic acid as a tool to study the mechanisms involved in Huntington's disease: past, present and future.” Molecules
15(2): 878–916.
10.3390/molecules15020878 Google Scholar
- Uchiyama, A., J. S. Kim, K. Kon, H. Jaeschke, K. Ikejima, S. Watanabe and J. J. Lemasters (2008). “Translocation of iron from lysosomes into mitochondria is a key event during oxidative stress-induced hepatocellular injury.” Hepatology 48(5): 1644–1654.
- Waldmeier, P. C., K. Zimmermann, T. Qian, M. Tintelnot-Blomley and J. J. Lemasters (2003). “Cyclophilin D as a drug target.” Curr Med Chem 10(16): 1485–1506.
- Wieder, E. D., H. Hang and M. H. Fox (1993). “Measurement of intracellular pH using flow cytometry with carboxy-SNARF-1.” Cytometry 14(8): 916–921.
- Zahrebelski, G., A. L. Nieminen, K. Al Ghoul, T. Qian, B. Herman and J. J. Lemasters (1995). “Progression of subcellular changes during chemical hypoxia to cultured rat hepatocytes: a laser scanning confocal microscopic study.” Hepatology 21(5): 1361–1372.
- Zhang, X. and J. J. Lemasters (2013). “Translocation of iron from lysosomes to mitochondria during ischemia predisposes to injury after reperfusion in rat hepatocytes.” Free Radic Biol Med 63: 243–253.
