Quantitative analysis of mitochondrial morphology and membrane potential in living cells using high-content imaging, machine learning, and morphological binning

Biochimica et Biophysica Acta - Molecular Cell Research

Volumn 1853, Issue 2, 2015, Pages 348-360

  Leonard, Anthony P ^a,b   Cameron, Robert B ^b   Speiser, Jaime L ^a   Wolf, Bethany J ^a   Peterson, Yuri K ^b   Schnellmann, Rick G ^b   Beeson, Craig C ^b   Rohrer, Bärbel ^a,c  

^a MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^b MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^c Ralph H Johnson Memorial Veteran's Administration Hospital   (United States)

Author keywords

High content microscopy; Image cytometry; Mitochondrial dynamics; Mitochondrial function; Mitochondrial toxicology; Morphometry

Indexed keywords

CARBONYL CYANIDE 4 (TRIFLUOROMETHOXY)PHENYLHYDRAZONE; OLIGOMYCIN; OUABAIN; ROTENONE; TERT BUTYL HYDROPEROXIDE; TETRAMETHYLRHODAMINE METHYL ESTER; ADENOSINE TRIPHOSPHATASE (POTASSIUM SODIUM); CARBONYL CYANIDE CHLOROPHENYLHYDRAZONE; CARBONYLCYANIDE 4-TRIFLUOROMETHOXYPHENYLHYDRAZONE; OXIDIZING AGENT;

ARTICLE; CONTROLLED STUDY; ENZYME PHOSPHORYLATION; FLUORESCENCE MICROSCOPY; HUMAN; HUMAN CELL; IMAGING; MACHINE LEARNING; MITOCHONDRIAL DYNAMICS; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRIAL RESPIRATION; MITOCHONDRION SWELLING; MORPHOLOGY; OXIDATIVE STRESS; PHENOTYPE; PHOTORECEPTOR CELL; QUANTITATIVE ANALYSIS; RESPIRATORY CHAIN; RESPIROMETRY; ANALOGS AND DERIVATIVES; ANIMAL; ARTIFICIAL INTELLIGENCE; CELL LINE; CELL MEMBRANE; CELL RESPIRATION; CELL SURVIVAL; DRUG EFFECTS; ELECTRON TRANSPORT; METABOLISM; MITOCHONDRION; MOUSE; PHYSIOLOGICAL STRESS; PROCEDURES; THREE DIMENSIONAL IMAGING;

ANIMALS; ARTIFICIAL INTELLIGENCE; CARBONYL CYANIDE M-CHLOROPHENYL HYDRAZONE; CELL LINE; CELL MEMBRANE; CELL RESPIRATION; CELL SURVIVAL; ELECTRON TRANSPORT; IMAGING, THREE-DIMENSIONAL; MEMBRANE POTENTIAL, MITOCHONDRIAL; MICE; MITOCHONDRIA; OXIDANTS; PHENOTYPE; SODIUM-POTASSIUM-EXCHANGING ATPASE; STRESS, PHYSIOLOGICAL; TERT-BUTYLHYDROPEROXIDE;

EID: 84913580346     PISSN: 01674889     EISSN: 18792596     Source Type: Journal    
DOI: 10.1016/j.bbamcr.2014.11.002     Document Type: Article

References (60)

1. Youle R.J., van der Bliek A.M. Mitochondrial fission, fusion, and stress. Science 2012, 337:1062-1065.
2. Zhan M., Brooks C., Liu F., Sun L., Dong Z. Mitochondrial dynamics: regulatory mechanisms and emerging role in renal pathophysiology. Kidney Int. 2013, 83:568-581.
3. Leonard A.P., Appleton K.M., Luttrell L.M., Peterson Y.K. A high-content, live-cell, and real-time approach to the quantitation of ligand-induced beta-Arrestin2 and Class A/Class B GPCR mobilization. Microsc. Microanal. 2013, 19:150-170.
4. Chevrollier A., Cassereau J., Ferre M., Alban J., Desquiret-Dumas V., Gueguen N., Amati-Bonneau P., Procaccio V., Bonneau D., Reynier P. Standardized mitochondrial analysis gives new insights into mitochondrial dynamics and OPA1 function. Int. J. Biochem. Cell Biol. 2012, 44:980-988.
5. Peng J.Y., Lin C.C., Chen Y.J., Kao L.S., Liu Y.C., Chou C.C., Huang Y.H., Chang F.R., Wu Y.C., Tsai Y.S., Hsu C.N. Automatic morphological subtyping reveals new roles of caspases in mitochondrial dynamics. PLoS Comput. Biol. 2011, 7:e1002212.
6. Lihavainen E., Mäkelä J., Spelbrink J.N., Ribeiro A.S. Mytoe: automatic analysis of mitochondrial dynamics. Bioinformatics 2012, 28:1050-1051.
7. Reis Y., Bernardo-Faura M., Richter D., Wolf T., Brors B., Hamacher-Brady A., Eils R., Brady N.R. Multi-parametric analysis and modeling of relationships between mitochondrial morphology and apoptosis. PLoS ONE 2012, 7:e28694.
8. Koopman W.J., Visch H.J., Smeitink J.A., Willems P.H. Simultaneous quantitative measurement and automated analysis of mitochondrial morphology, mass, potential, and motility in living human skin fibroblasts. Cytometry A 2006, 69:1-12.
9. Hothorn T., Hornik K., Zeileis A. Unbiased recursive partitioning: a conditional inference framework. J. Comput. Graph. Stat. 2006, 15:651-674.
10. al-Ubaidi M.R., Font R.L., Quiambao A.B., Keener M.J., Liou G.I., Overbeek P.A., Baehr W. Bilateral retinal and brain tumors in transgenic mice expressing simian virus 40 large T antigen under control of the human interphotoreceptor retinoid-binding protein promoter. J. Cell Biol. 1992, 119:1681-1687.
11. Maarten G.M.C., Taal W., Marsden Philip A., Skorecki Karl, Yu Alan S.L., Brenner Barry M. Anatomy of the kidney. Brenner and Rector's the Kidney 2012, Elsevier Saunders, (Place Published). M.W. Taal (Ed.).
12. Robert I., Marks J. 6.2.1 The Nyquist Density, Introduction to Shannon Sampling and Interpolation Theory 1991, 322. Springer Verlag, (Place Published).
13. Collins T.J., Berridge M.J., Lipp P., Bootman M.D. Mitochondria are morphologically and functionally heterogeneous within cells. EMBO J. 2002, 21:1616-1627.
14. Therneau T. rpart: recursive partitioning. Recursive Partitioning and Regression Trees 2013, pp.
15. Breiman L. Random forests. A Description of the Random Forest Algorithm for Machine Learning-based Classification 2004, pp.
16. Clayden J. RNiftyReg. RNiftyReg: Medical Image Registration Using the NiftyReg Library 2013, pp., (Based on original code by Marc Modat and Pankaj Daga).
17. Bates D. R: A Language and Environment for Statistical Computing 2013, pp., R Foundation for Statistical Computing, Vienna, Austria.
18. Ferrick D.A., Neilson A., Beeson C. Advances in measuring cellular bioenergetics using extracellular flux. Drug Discov. Today 2008, 13:268-274.
19. Lenth R. Java Applets for Power and Sample Size University of Iowa. Java Applets for Power and Sample Size 2006-2009, pp.
20. Steyerberg E.W., Bleeker S.E., Moll H.A., Grobbee D.E., Moons K.G. Internal and external validation of predictive models: a simulation study of bias and precision in small samples. J. Clin. Epidemiol. 2003, 56:441-447.
21. Van Houwelingen J.C., Le Cessie S. Predictive value of statistical models. Stat. Med. 1990, 9:1303-1325.
22. Funk J.A., Odejinmi S., Schnellmann R.G. SRT1720 induces mitochondrial biogenesis and rescues mitochondrial function after oxidant injury in renal proximal tubule cells. J. Pharmacol. Exp. Ther. 2010, 333:593-601.
23. Kakkar P., Mehrotra S., Viswanathan P.N. tBHP induced in vitro swelling of rat liver mitochondria. Mol. Cell. Biochem. 1996, 154:39-45.
24. Masaki N., Kyle M.E., Serroni A., Farber J.L. Mitochondrial damage as a mechanism of cell injury in the killing of cultured hepatocytes by tert-butyl hydroperoxide. Arch. Biochem. Biophys. 1989, 270:672-680.
25. Perron N.R., Beeson C., Rohrer B. Early alterations in mitochondrial reserve capacity; a means to predict subsequent photoreceptor cell death. J. Bioenerg. Biomembr. 2013, 45:101-109.
26. Koopman W.J., Nijtmans L.G., Dieteren C.E., Roestenberg P., Valsecchi F., Smeitink J.A., Willems P.H. Mammalian mitochondrial complex I: biogenesis, regulation and reactive oxygen species generation. Antioxid. Redox Signal. 2010, 12:1431-1470.
27. Rieske J.S. Changes in oxidation-reduction potential of cytochrome b observed in the presence of antimycin A. Arch. Biochem. Biophys. 1971, 145:179-193.
28. Symersky J., Osowski D., Walters D.E., Mueller D.M. Oligomycin frames a common drug-binding site in the ATP synthase. Proc. Natl. Acad. Sci. U. S. A. 2012, 109:13961-13965.
29. Pilati C.F., Paradise N.F. Ouabain-induced mechanical toxicity: aberrations in left ventricular function, calcium concentration, and ultrastructure. Proc. Soc. Exp. Biol. Med. 1984, 175:342-350.
30. Beeson C.C., Beeson G.C., Schnellmann R.G. A high-throughput respirometric assay for mitochondrial biogenesis and toxicity. Anal. Biochem. 2010, 404:75-81.
31. Lemasters J.J., Chacon E., Ohata H., Harper I.S., Nieminen A.L., Tesfai S.A., Herman B. Measurement of electrical potential, pH, and free calcium ion concentration in mitochondria of living cells by laser scanning confocal microscopy. Methods Enzymol. 1995, 260:428-444.
32. Distelmaier F., Koopman W.J., Testa E.R., de Jong A.S., Swarts H.G., Mayatepek E., Smeitink J.A., Willems P.H. Life cell quantification of mitochondrial membrane potential at the single organelle level. Cytometry A 2008, 73:129-138.
33. Lemasters J.J., Nieminen A.L., Qian T., Trost L.C., Elmore S.P., Nishimura Y., Crowe R.A., Cascio W.E., Bradham C.A., Brenner D.A., Herman B. The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy. Biochim. Biophys. Acta 1998, 1366:177-196.
34. Saunders J.E., Beeson C.C., Schnellmann R.G. Characterization of functionally distinct mitochondrial subpopulations. J. Bioenerg. Biomembr. 2013, 45:87-99.
35. Cook G. Enamines: Synthesis: Structure, and Reactions 1987, Taylor & Francis, (Place Published). Second edition.
36. Thompson C.M. Detecting a cell using image segmentation, MathWorks. MATLAB Version R2013a Documentation, Image Processing Toolbox, Image Processing Toolbox Examples 2013, pp.
37. Buades A., Coll B., Morel J. A review of image denoising algorithms, with a new one. Multiscale Model. Simul. 2005, 4:490-530.
38. Suranyi E.M., Avi-Dor Y. Effect of potassium and ouabain on swelling of rat liver mitochondria. Biochem. Biophys. Res. Commun. 1965, 19:215-230.
39. Blondin G.A., Green D.E. The mechanism of mitochondrial swelling. Proc. Natl. Acad. Sci. U. S. A. 1967, 58:612-619.
40. Pletjushkina O.Y., Lyamzaev K.G., Popova E.N., Nepryakhina O.K., Ivanova O.Y., Domnina L.V., Chernyak B.V., Skulachev V.P. Effect of oxidative stress on dynamics of mitochondrial reticulum. Biochim. Biophys. Acta 2006, 1757:518-524.
41. Yamano K., Youle R.J. Coupling mitochondrial and cell division. Nat. Cell Biol. 2011, 13:1026-1027.
42. Distelmaier F., Valsecchi F., Forkink M., van Emst-de Vries S., Swarts H.G., Rodenburg R.J., Verwiel E.T., Smeitink J.A., Willems P.H., Koopman W.J. Trolox-sensitive reactive oxygen species regulate mitochondrial morphology, oxidative phosphorylation and cytosolic calcium handling in healthy cells. Antioxid. Redox Signal. 2012, 17:1657-1669.
43. Lemasters J.J. Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging. Rejuvenation Res. 2005, 8:3-5.
44. Lemasters J.J., Theruvath T.P., Zhong Z., Nieminen A.L. Mitochondrial calcium and the permeability transition in cell death. Biochim. Biophys. Acta 2009, 1787:1395-1401.
45. Wang X., Jian C., Zhang X., Huang Z., Xu J., Hou T., Shang W., Ding Y., Zhang W., Ouyang M., Wang Y., Yang Z., Zheng M., Cheng H. Superoxide flashes: elemental events of mitochondrial ROS signaling in the heart. J. Mol. Cell. Cardiol. 2012, 52:940-948.
46. Youle R.J., Karbowski M. Mitochondrial fission in apoptosis. Nat. Rev. Mol. Cell Biol. 2005, 6:657-663.
47. Han Y.H., Kim S.H., Kim S.Z., Park W.H. Carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP) as an O2(-) generator induces apoptosis via the depletion of intracellular GSH contents in Calu-6 cells. Lung Cancer 2009, 63:201-209.
48. Otera H., Wang C., Cleland M.M., Setoguchi K., Yokota S., Youle R.J., Mihara K. Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells. J. Cell Biol. 2010, 191:1141-1158.
49. Baudry J.P., Raftery A.E., Celeux G., Lo K., Gottardo R. Combining mixture components for clustering. J. Comput. Graph. Stat. 2010, 9:332-353.
50. Wouters F.S. Imaging molecular physiology in cells using FRET-Based fluorescent nanosensors. Optical Fluorescence Microscopy 2011, 131-152. Springer, Berlin Heidelberg, (Place Published). A. Diaspro (Ed.).
51. Wills L.P., Beeson G.C., Trager R.E., Lindsey C.C., Beeson C.C., Peterson Y.K., Schnellmann R.G. High-throughput respirometric assay identifies predictive toxicophore of mitochondrial injury. Toxicol. Appl. Pharmacol. 2013, 272:490-502.
52. Orvedahl A., Sumpter R., Xiao G., Ng A., Zou Z., Tang Y., Narimatsu M., Gilpin C., Sun Q., Roth M., Forst C.V., Wrana J.L., Zhang Y.E., Luby-Phelps K., Xavier R.J., Xie Y., Levine B. Image-based genome-wide siRNA screen identifies selective autophagy factors. Nature 2011, 480:113-117.
53. Hasson S.A., Kane L.A., Yamano K., Huang C.H., Sliter D.A., Buehler E., Wang C., Heman-Ackah S.M., Hessa T., Guha R., Martin S.E., Youle R.J. High-content genome-wide RNAi screens identify regulators of parkin upstream of mitophagy. Nature 2013, 504(7479):291-295.
54. Gomes L.C., Scorrano L. Mitochondrial morphology in mitophagy and macroautophagy. Biochim. Biophys. Acta (BBA) Mol. Cell Res. 2013, 1833:205-212.
55. Jäger S., Bucci C., Tanida I., Ueno T., Kominami E., Saftig P., Eskelinen E.-L. Role for Rab7 in maturation of late autophagic vacuoles. J. Cell Sci. 2004, 117:4837-4848.
56. Suen D.F., Narendra D.P., Tanaka A., Manfredi G., Youle R.J. Parkin overexpression selects against a deleterious mtDNA mutation in heteroplasmic cybrid cells. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:11835-11840.
57. Lightowlers R.N., Chinnery P.F., Turnbull D.M., Howell N. Mammalian mitochondrial genetics: heredity, heteroplasmy and disease. Trends Genet. 1997, 13:450-455.
58. Carelli V., La Morgia C., Valentino M.L., Barboni P., Ross-Cisneros F.N., Sadun A.A. Retinal ganglion cell neurodegeneration in mitochondrial inherited disorders. Biochim. Biophys. Acta 2009, 1787:518-528.
59. Amiott E.A., Lott P., Soto J., Kang P.B., McCaffery J.M., DiMauro S., Abel E.D., Flanigan K.M., Lawson V.H., Shaw J.M. Mitochondrial fusion and function in Charcot-Marie-Tooth type 2A patient fibroblasts with mitofusin 2 mutations. Exp. Neurol. 2008, 211:115-127.
60. Valsecchi F., Grefte S., Roestenberg P., Joosten-Wagenaars J., Smeitink J.A., Willems P.H., Koopman W.J. Primary fibroblasts of NDUFS4(-/-) mice display increased ROS levels and aberrant mitochondrial morphology. Mitochondrion 2012, 13:436-443.