Mitochondrial Dysfunction and Neurodegeneration in Lysosomal Storage Disorders

Trends in Molecular Medicine

Volumn 23, Issue 2, 2017, Pages 116-134

  Plotegher, Nicoletta ^a   Duchen, Michael R ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CALCIUM; LYSOSOMAL PROTEINS; PROTEIN;

AUTOPHAGY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; HUMAN; LYSOSOME STORAGE DISEASE; MACROMOLECULE; MEMBRANE POTENTIAL; MITOCHONDRIAL RESPIRATION; MITOCHONDRION; MITOPHAGY; MOLECULE; NERVE DEGENERATION; NONHUMAN; OXIDATIVE STRESS; PATHOPHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; COMPLICATION; GENETICS; LYSOSOME; METABOLISM; MUTATION; NEURODEGENERATIVE DISEASES; PATHOLOGY;

ANIMALS; HUMANS; LYSOSOMAL STORAGE DISEASES; LYSOSOMES; MITOCHONDRIA; MUTATION; NEURODEGENERATIVE DISEASES; PROTEINS;

EID: 85009818515     PISSN: 14714914     EISSN: 1471499X     Source Type: Journal    
DOI: 10.1016/j.molmed.2016.12.003     Document Type: Review

References (131)

1. 1 Platt, F.M., et al. Lysosomal storage disorders: the cellular impact of lysosomal dysfunction. J Cell Biol 199 (2012), 723–734.
2. 2 Meikle, P.J., et al. Prevalence of lysosomal storage disorders. JAMA 281 (1999), 249–254.
3. 3 Poupětová, H., et al. The birth prevalence of lysosomal storage disorders in the Czech Republic: comparison with data in different populations. J Inherit Metab Dis 33 (2010), 387–396.
4. 4 Verity, C., et al. The epidemiology of progressive intellectual and neurological deterioration in childhood. Arch Dis Child 95 (2010), 361–364.
5. 5 Parenti, G., et al. Lysosomal storage diseases: from pathophysiology to therapy. Annu Rev Med 66 (2015), 471–486.
6. 6 Keilani, S., et al. Lysosomal dysfunction in a mouse model of Sandhoff disease leads to accumulation of ganglioside-bound amyloid-beta peptide. J Neurosci 32 (2012), 5223–5236.
7. 7 Lloyd-Evans, E., Haslett, L.J., The lysosomal storage disease continuum with ageing-related neurodegenerative disease. Ageing Res Rev 32 (2016), 104–121.
8. 8 Kresojevic, N., et al. Mutations in Niemann–Pick type C gene are risk factor for Alzheimer's disease. Med Hypotheses J 83 (2014), 559–562.
9. 2+ homeostasis via TRPML1 by regulating vATPase-mediated lysosome acidification. Cell Rep 12 (2015), 1430–1444.
10. 10 Sidransky, E., et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease. N Engl J Med 361 (2009), 1651–1661.
11. 11 Osellame, L.D., et al. Mitochondria and quality control defects in a mouse model of Gaucher disease—links to Parkinson's disease. Cell Metab 17 (2013), 941–953.
12. 12 Mazzulli, J.R., et al. Gaucher disease glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell 146 (2011), 37–52.
13. 13 Bae, E.-J., et al. Glucocerebrosidase depletion enhances cell-to-cell transmission of α-synuclein. Nat Commun, 5, 2014, 4755.
14. 14 Cullen, V., et al. Acid β-glucosidase mutants linked to Gaucher disease, Parkinson disease, and Lewy body dementia alter α-synuclein processing. Ann Neurol 69 (2011), 940–953.
15. 15 Murphy, K.E., et al. Reduced glucocerebrosidase is associated with increased α-synuclein in sporadic Parkinson's disease. Brain 137 (2014), 834–848.
16. 16 Bae, E.-J., et al. Loss of glucocerebrosidase 1 activity causes lysosomal dysfunction and α-synuclein aggregation. Exp Mol Med, 47, 2015, e153.
17. 17 Almeida, A., et al. Different responses of astrocytes and neurons to nitric oxide: the role of glycolytically generated ATP in astrocyte protection. Proc Natl Acad Sci U S A 98 (2001), 15294–15299.
18. 18 Soubannier, V., et al. A vesicular transport pathway shuttles cargo from mitochondria to lysosomes. Curr Biol 22 (2012), 135–141.
19. 19 Siddiqui, A., et al. Mitochondrial quality control via the PGC1α–TFEB signaling pathway is compromised by parkin Q311X mutation but independently restored by rapamycin. J Neurosci 35 (2015), 12833–12844.
20. 20 Settembre, C., et al. TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop. Nat Cell Biol 15 (2013), 647–658.
21. 21 Scarpulla, R.C., Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network. BBA – Mol Cell Res 1813 (2011), 1269–1278.
22. 22 Vega, R.B., et al. The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol Cell Biol 20 (2000), 1868–1876.
23. 23 Baixauli, F., et al. Mitochondrial respiration controls lysosomal function during inflammatory T cell responses article mitochondrial respiration controls lysosomal function during inflammatory T cell responses. Cell Metab 22 (2015), 485–498.
24. 24 Demers-Lamarche, J., Loss of mitochondrial function impairs lysosomes. J Biol Chem 291 (2016), 10263–10276.
25. 25 Kim, J., et al. AMPK activators: mechanisms of action and physiological activities. Exp Mol Med 48 (2016), 1–12.
26. 26 Settembre, C., et al. TFEB links autophagy to lysosomal biogenesis. Science 332 (2010), 1429–1433.
27. 27 Settembre, C., et al. A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB open. EMBO J 31 (2012), 1095–1108.
28. 28 Martina, J.A., et al. MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB. Autophagy 8 (2012), 903–914.
29. 29 Jin, R.U., Mills, J.C., RAB26 coordinates lysosome traffic and mitochondrial localization. J Cell Sci 127 (2014), 1018–1032.
30. 30 Suzuki, K., et al. Accumulated α-synuclein affects the progression of GM2 gangliosidoses. Exp Neurol 284 (2016), 38–49.
31. 31 de la Mata, M., et al. Pharmacological chaperones and coenzyme Q10 treatment improves mutant β-glucocerebrosidase activity and mitochondrial function in neuronopathic forms of Gaucher disease. Sci Rep 5 (2015), 1–18.
32. 32 Vilaca, R., et al. Sphingolipid signalling mediates mitochondrial dysfunctions and reduced chronological lifespan in the yeast model of Niemann–Pick type C1. Mol Microbiol 91 (2014), 438–451.
33. 33 Woś, M., et al. Mitochondrial dysfunction in fibroblasts derived from patients with Niemann–Pick type C disease. Arch Biochem Biophys 593 (2016), 50–59.
34. 34 Visentin, S., et al. The stimulation of adenosine A2A receptors ameliorates the pathological phenotype of fibroblasts from Niemann–Pick type C patients. J Neurosci 33 (2013), 15388–15393.
35. 35 Ordonez, M.P., et al. Disruption and therapeutic rescue of autophagy in a human neuronal model of Niemann–Pick type C1. Hum Mol Genet 21 (2012), 2651–2662.
36. 36 Yu, W., et al. Altered cholesterol metabolism in Niemann–Pick type C1 mouse brains affects mitochondrial function. J Biol Chem 280 (2005), 11731–11739.
37. 37 Settembre, C., et al. A block of autophagy in lysosomal storage disorders. Hum Mol Genet 17 (2008), 119–129.
38. 38 de Pablo-Latorre, R., Impaired parkin-mediated mitochondrial targeting to autophagosomes differentially contributes to tissue pathology in lysosomal storage diseases. Hum Mol Genet 21 (2012), 1770–1781.
39. 39 Takamura, A., et al. Enhanced autophagy and mitochondrial aberrations in murine GM1-gangliosidosis. Biochem Biophys Res Commun 367 (2008), 616–622.
40. 40 Martins, C., et al. Neuroinflammation, mitochondrial defects and neurodegeneration in mucopolysaccharidosis III type C mouse model. Brain 138 (2015), 336–355.
41. 41 Das, A.M., et al. Anomalies of mitochondrial ATP synthase regulation in four different types of neuronal ceroid lipofuscinosis. Mol Genet Metab 66 (1999), 349–355.
42. 42 Jolly, R.D., et al. Mitochondrial dysfunction in the neuronal ceroid-lipofuscinoses (Batten disease). Neurochem Int 40 (2002), 565–571.
43. 43 Lojewski, X., et al. Human iPSC models of neuronal ceroid lipofuscinosis capture distinct effects of TPP1 and CLN3 mutations on the endocytic pathway. Hum Mol Genet 23 (2014), 2005–2022.
44. 44 Fossale, E., et al. Membrane trafficking and mitochondrial abnormalities precede subunit c deposition in a cerebellar cell model of juvenile neuronal ceroid lipofuscinosis. BMC Neurosci, 5, 2004, 57.
45. 45 Luiro, K., et al. Batten disease (JNCL) is linked to disturbances in mitochondrial, cytoskeletal, and synaptic compartments. J Neurosci Res 84 (2006), 1124–1138.
46. 46 Kang, S., et al. Batten disease is linked to altered expression of mitochondria-related metabolic molecules. Neurochem Int 62 (2013), 931–935.
47. 47 Pezzini, F., et al. Involvement of the mitochondrial compartment in human NCL fibroblasts. Biochem Biophys Res Commun 416 (2011), 159–164.
48. 48 Burrow, T.A., et al. Acute progression of neuromuscular findings in infantile Pompe disease. Pediatr Neurol 42 (2010), 455–458.
49. Neo Pompe disease mice. J Neuropathol Exp Neurol 67 (2008), 803–818.
50. 50 Raben, N., et al. Autophagy and mitochondria in Pompe disease: nothing is so new as what has long been forgotten. Am J Med Genet Part C Semin Med Genet 160C (2012), 13–21.
51. 51 Lim, J.A., et al. Defects in calcium homeostasis and mitochondria can be reversed in Pompe disease. Autophagy 8627 (2015), 37–41.
52. 52 Duchen, B.M.R., et al. Imaging mitochondrial function in intact cells. Methods Enzymol 361 (2003), 353–389.
53. 53 MacAskill, A.F., et al. Mitochondrial trafficking and the provision of energy and calcium buffering at excitatory synapses. Eur J Neurosci 32 (2010), 231–240.
54. 54 Saxton, W.M., Hollenbeck, P.J., The axonal transport of mitochondria. J Cell Sci 125 (2012), 2095–2104.
55. 55 Cantuti Castelvetri, L., The sphingolipid psychosine inhibits fast axonal transport in Krabbe disease by activation of GSK3β and deregulation of molecular motors. J Neurosci 33 (2013), 10048–10056.
56. 56 Cao, Y., et al. Autophagy is disrupted in a knock-in mouse model of juvenile neuronal ceroid lipofuscinosis. J Biol Chem 281 (2006), 20483–20493.
57. 57 Vidal-Donet, J.M., Alterations in ROS activity and lysosomal pH account for distinct patterns of macroautophagy in LINCL and JNCL fibroblasts. PLoS One, 8, 2013, e55526.
58. 58 Jennings, J.J., et al. Mitochondrial aberrations in mucolipidosis type IV. J Biol Chem 281 (2006), 39041–39050.
59. 59 Takikita, S., et al. Fiber type conversion by PGC-1alpha activates lysosomal and autophagosomal biogenesis in both unaffected and pompe skeletal muscle. PLoS One, 5, 2010, e15239.
60. 60 Twig, G., et al. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 27 (2008), 433–446.
61. 61 Priault, M., et al. Impairing the bioenergetic status and the biogenesis of mitochondria triggers mitophagy in yeast. Cell Death Differ 12 (2005), 1613–1621.
62. 62 Narendra, D., et al. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 183 (2008), 795–803.
63. 63 Narendra, D.P., et al. PINK1 is selectively stabilized on impaired mitochondria to activate parkin. Plos Biol, 8, 2010, e1000298.
64. 64 Wong, Y.C., Holzbaur, E.L.F., Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy that is disrupted by an ALS-linked mutation. Proc Natl Acad Sci U S A 111 (2014), e4439–4448.
65. 65 Hamacher-Brady, A., Brady, N.R., Mitophagy programs: mechanisms and physiological implications of mitochondrial targeting by autophagy. Cell Mol Life Sci 73 (2016), 775–795.
66. o-ATP synthase, defines mitochondrial volume fraction in HeLa cells by regulating autophagy. BBA – Bioenerg 1787 (2009), 393–401.
67. 67 Donida, B., et al. Oxidative stress and inflammation in mucopolysaccharidosis type IVA patients treated with enzyme replacement therapy. Biochim Biophys Acta 1852 (2015), 1012–1019.
68. 68 Zampieri, S., et al. Oxidative stress in NPC1 deficient cells: protective effect of allopregnanolone. J Cell Mol Med 13 (2009), 3786–3796.
69. 69 Vazquez, M.C., et al. Alteration of gene expression profile in Niemann–Pick type C mice correlates with tissue damage and oxidative stress. PLoS One, 6, 2011, e28777.
70. 70 Hachiya, Y., et al. Mechanisms of neurodegeneration in neuronal ceroid-lipofuscinoses. Acta Neuropathol 111 (2006), 168–177.
71. 71 Hawkins, K.E., et al. NRF2 orchestrates the metabolic shift during induced pluripotent stem cell reprogramming. Cell Rep 14 (2016), 1883–1891.
72. 72 Voccoli, V., et al. Role of extracellular calcium and mitochondrial oxygen species in psychosine-induced oligodendrocyte cell death. Cell Death Dis 5 (2014), e1529–10.
73. 73 Kennedy, B.E., et al. Pre-symptomatic activation of antioxidant responses and alterations in glucose and pyruvate metabolism in Niemann–Pick type C1-deficient murine brain. PLoS One, 8, 2013, e82685.
74. 74 Cologna, S.M., et al. Quantitative proteomic analysis of Niemann-Pick disease, type C1 cerebellum identifies protein biomarkers and provides pathological insight. PLoS One, 7, 2012, e47845.
75. 75 Llorente-Folch, I., The regulation of neuronal mitochondrial metabolism by calcium. J Physiol 593 (2015), 3447–3462.
76. 76 Garrity, A.G., et al. The endoplasmic reticulum, not the pH gradient, drives calcium refilling of lysosomes. Elife 5 (2016), 1–18.
77. 77 Pelled, D., et al. Enhanced calcium release in the acute neuronopathic form of Gaucher disease. Neurobiol Dis 18 (2005), 83–88.
78. 2+-ATPase in a mouse model of Sandhoff disease and prevention by treatment with n-butyldeoxynojirimycin. J Biol Chem 278 (2003), 29496–29501.
79. 2+ stores are remodelled in GBA1-linked Parkinson disease patient fibroblasts. Cell Calcium 59 (2015), 12–20.
80. mnd mouse model of neuronal ceroid lipofuscinosis. Cell Calcium 50 (2011), 491–501.
81. 81 Korkotian, E., et al. Elevation of intracellular glucosylceramide levels results in an increase in endoplasmic reticulum density and in functional calcium stores in cultured neurons. J Biol Chem 274 (1999), 21673–21678.
82. 82 Qiu, J., et al. Mitochondrial calcium uniporter Mcu controls excitotoxicity and is transcriptionally repressed by neuroprotective nuclear calcium signals. Nat Commun 4 (2013), 1–12.
83. 2+-dependent mitochondrial apoptosis. Mol Cell 36 (2009), 500–511.
84. 84 Zhang, X., et al. MCOLN1 is a ROS sensor in lysosomes that regulates autophagy. Nat Commun 7 (2016), 1–12.
85. 85 Wang, W., et al. Up-regulation of lysosomal TRPML1 channels is essential for lysosomal adaptation to nutrient starvation. Proc Natl Acad Sci 112 (2015), E1373–E1381.
86. 2+ influx. J Cell Sci 129 (2016), 3859–3867.
87. 87 Lloyd-evans, E., et al. Niemann–Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium. Nat Med 14 (2010), 1247–1256.
88. 88 Hoglinger, D., et al. Intracellular sphingosine releases calcium from lysosomes. Elife 4 (2015), 1–20.
89. 89 Jung, T., et al. Lipofuscin formation, distribution, and metabolic consequences. Ann N Y Acad Sci 1119 (2007), 97–111.
90. 90 Elleder, M., et al. Follow-up study of subunit c of mitochondrial ATP synthase (SCMAS) in Batten disease and in unrelated lysosomal disorders. Acta Neuropathol 93 (1997), 379–390.
91. 91 Palmer, D.N., et al. Mitochondrial ATP synthase subunit c storage in the ceroid-lipofuscinoses (Batten disease). Am J Med Genet 42 (1992), 561–567.
92. 92 Clayton, D.F., George, J.M., Synucleins in synaptic plasticity and neurodegenerative disorders. J Neurosci Res 58 (1999), 120–129.
93. 93 Plotegher, N., et al. Biophysical groundwork as a hinge to unravel the biology of α-synuclein aggregation and toxicity. Q Rev Biophys 1 (2014), 1–48.
94. 94 Plotegher, N., et al. Number and brightness analysis of alpha-synuclein oligomerization and the associated mitochondrial morphology alterations in live cells. Biochim Biophys Acta – Gen Subj 1840 (2014), 2014–2024.
95. 95 Nakamura, K., et al. Direct membrane association drives mitochondrial fission by the Parkinson disease-associated protein α-synuclein. J Biol Chem 286 (2011), 20710–20726.
96. 96 Li, L., et al. Human A53T α-synuclein causes reversible deficits in mitochondrial function and dynamics in primary mouse cortical neurons. PLoS One 8 (2013), 1–14.
97. 97 Nakamura, K., et al. Optical reporters for the conformation of alpha-synuclein reveal a specific interaction with mitochondria. J Neurosci 28 (2008), 12305–12317.
98. 2+ is a key factor in α-synuclein-induced neurotoxicity. J Cell Sci 129 (2016), 1792–1801.
99. 99 Song, J., et al. HMGB1 is involved in autophagy inhibition caused by SNCA/alpha-synuclein overexpression. Autophagy 10 (2014), 144–154.
100. 100 Winslow, A.R., et al. Alpha-synuclein impairs macroautophagy: implications for Parkinson's disease. J Cell Biol 190 (2010), 1023–1037.
101. 101 Choi, J.H., et al. Aggregation of alpha-synuclein in brain samples from subjects with glucocerebrosidase mutations. Mol Genet Metab 104 (2011), 185–188.
102. 102 Suzuki, K., et al. Neuronal and glial accumulation of alpha- and beta-synucleins in human lipidoses. Acta Neuropathol 114 (2007), 481–489.
103. 103 Tolnay, M.G.S.M., Goedert, S.L.M., Microtubule-associated protein tau, heparan sulphate and α-synuclein in several neurodegenerative diseases with dementia. Acta Neuropathol 97 (1999), 585–594.
104. 104 Hamano, K., et al. Mechanisms of neurodegeneration in mucopolysaccharidoses II and IIIB: analysis of human brain tissue. Acta Neuropathol 115 (2008), 547–559.
105. 105 Pchelina, S.N., et al. Increased plasma oligomeric alpha-synuclein in patients with lysosomal storage diseases. Neurosci Lett 583 (2014), 188–193.
106. 106 Kang, S., et al. Altered levels of α-synuclein and sphingolipids in Batten disease lymphoblast cells. Gene 539 (2014), 181–185.
107. 107 Kelly, J.M., et al. Emerging therapies for neuropathic lysosomal storage disorders. Prog Neurobiol, 2016, 2016, 10.1016/j.pneurobio.2016.10.002 Published online October 8.
108. 108 Zheng, X., et al. Alleviation of neuronal energy deficiency by mTOR inhibition as a treatment for mitochondria-related neurodegeneration. Elife 5 (2016), 1–23.
109. 109 Sardiello, M., et al. A gene network regulating lysosomal biogenesis and function. Science 325 (2009), 473–477.
110. 110 Du, T.T., et al. GBA deficiency promotes SNCA/alpha-synuclein accumulation through autophagic inhibition by inactivated PPP2A. Autophagy 11 (2015), 1803–1820.
111. 111 Sarkar, S., et al. Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein. J Biol Chem 282 (2007), 5641–5652.
112. 112 Lindström, V., et al. Immunotherapy targeting α-synuclein protofibrils reduced pathology in (Thy-1)–h[A30P] α-synuclein mice. Neurobiol Dis 69 (2014), 134–143.
113. 113 Games, D., et al. Reducing C-terminal-truncated alpha-synuclein by immunotherapy attenuates neurodegeneration and propagation in Parkinson's disease-like models. Proc Natl Acad Sci U S A 34 (2014), 9441–9454.
114. 114 Mindell, J.A., Lysosomal acidification mechanisms. Annu Rev Physiol 74 (2012), 69–86.
115. 115 Ohkuma, S., et al. Identification and characterization of a proton pump on lysosomes by fluorescein isothiocyanate-dextran fluorescence. Proc Natl Acad Sci U S A 79 (1982), 2758–2762.
116. + antiporter ClC-7 is the primary chloride permeation pathway in lysosomes. Nature 453 (2008), 788–792.
117. + channel regulating lysosomal function. Cell 162 (2015), 1101–1112.
118. + channels to adapt to metabolic state. Cell 152 (2013), 778–790.
119. 119 Soyombo, A.A., et al. TRP-ML1 regulates lysosomal pH and acidic lysosomal lipid hydrolytic activity. J Biol Chem 281 (2006), 7294–7301.
120. 120 Lu, Y., et al. Two pore channel 2 (TPC2) inhibits autophagosomal–lysosomal fusion by alkalinizing lysosomal pH. J Biol Chem 288 (2013), 24247–24263.
121. 121 Braulke, T., Bonifacino, J.S., Sorting of lysosomal proteins. BBA – Mol Cell Res 1793 (2009), 605–614.
122. 122 Settembre, C., et al. Signals from the lysosome: a control centre for cellular clearance and energy metabolism. Nature 14 (2013), 283–296.
123. 123 Medina, D.L., et al. Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB. Nat Cell Biol 17 (2015), 288–299.
124. 124 De Stefani, D., et al. A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 476 (2011), 336–340.
125. 125 Bernardi, P., et al. The mitochondrial permeability transition pore: channel formation by F-ATP synthase, integration in signal transduction and role in pathophysiology. Physiol Rev 95 (2015), 1111–1155.
126. 126 Konig, T., et al. The m-AAA protease associated with neurodegeneration limits MCU activity in mitochondria. Mol Cell 64 (2016), 148–162.
127. 127 Hoffman, N.E., et al. MICU1 motifs define mitochondrial calcium uniporter binding and activity. Cell Rep 5 (2013), 1576–1588.
128. 128 Tomar, D., et al. MCUR1 is a scaffold factor for the MCU complex function and promotes mitochondrial bioenergetics. Cell Rep 15 (2016), 1673–1685.
129. 129 Lehmann, G., et al. On the linkage between the ubiquitin-proteasome system and the mitochondria. Biochem Biophys Res Commun 473 (2016), 80–86.
130. 130 Lemasters, J.J., Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging. Rejuvenation Res 8 (2005), 3–5.
131. 131 Hynes, J., Carey, C., High-throughput real-time analysis of cell oxygenation using intracellular oxygen-sensitive probes. Methods Mol Biol 1264 (2015), 203–217.