Reactive oxygen species and mitochondrial dynamics: The yin and yang of mitochondrial dysfunction and cancer progression

Antioxidants

Volumn 7, Issue 1, 2018, Pages

  Ježek, Jan ^a   Cooper, Katrina F ^a   Strich, Randy ^a  

^a ROWAN UNIVERSITY   (United States)

Author keywords

Cancer; Mitochondrial dynamics; Mitochondrial ultrastructure; Oxidative stress; Reactive oxygen species; Redox signaling; Superoxide

Indexed keywords

EID: 85041002780     PISSN: None     EISSN: 20763921     Source Type: Journal    
DOI: 10.3390/antiox7010013     Document Type: Review

References (228)

1. Nicholls, D.G.; Ferguson, S.J. Bioenergetics, 4th ed.; Academic Press, Elsevier: Amsterdam, The Netherlands, 2013; 419p.
2. Rongvaux, A. Innate immunity and tolerance toward mitochondria. Mitochondrion 2017.
3. Munoz-Gomez, S.A.; Wideman, J.G.; Roger, A.J.; Slamovits, C.H. The origin of mitochondrial cristae from alphaproteobacteria. Mol. Biol. Evol. 2017, 34, 943–956.
4. Zorov, D.B.; Plotnikov, E.Y.; Silachev, D.N.; Zorova, L.D.; Pevzner, I.B.; Zorov, S.D.; Babenko, V.A.; Jankauskas, S.S.; Popkov, V.A.; Savina, P.S. Microbiota and mitobiota. Putting an equal sign between mitochondria and bacteria. Biochemistry 2014, 79, 1017–1031.
5. Willems, P.H.; Rossignol, R.; Dieteren, C.E.; Murphy, M.P.; Koopman, W.J. Redox homeostasis and mitochondrial dynamics. Cell Metab. 2015, 22, 207–218.
6. Mishra, P.; Chan, D.C. Metabolic regulation of mitochondrial dynamics. J. Cell Biol. 2016, 212, 379–387.
7. Melkov, A.; Abdu, U. Regulation of long-distance transport of mitochondria along microtubules. Cell. Mol. Life Sci. 2017.
8. Wu, M.; Kalyanasundaram, A.; Zhu, J. Structural and biomechanical basis of mitochondrial movement in eukaryotic cells. Int. J. Nanomed. 2013, 8, 4033–4042.
9. Berridge, M.V.; Neuzil, J. The mobility of mitochondria: Intercellular trafficking in health and disease. Clin. Exp. Pharmacol. Physiol. 2017.
10. Tang, B.L. MIRO GTPases in mitochondrial transport, homeostasis and pathology. Cells 2016, 5, 1.
11. Harbauer, A.B. Mitochondrial health maintenance in axons. Biochem. Soc. Trans. 2017, 45, 1045–1052.
12. Altieri, D.C. Mitochondria on the move: Emerging paradigms of organelle trafficking in tumour plasticity and metastasis. Br. J. Cancer 2017, 117, 301–305.
13. Pendin, D.; Filadi, R.; Pizzo, P. The concerted action of mitochondrial dynamics and positioning: New characters in cancer onset and progression. Front. Oncol. 2017, 7, 102.
14. Cao, Y.L.; Meng, S.; Chen, Y.; Feng, J.X.; Gu, D.D.; Yu, B.; Li, Y.J.; Yang, J.Y.; Liao, S.; Chan, D.C.; et al. Mfn1 structures reveal nucleotide-triggered dimerization critical for mitochondrial fusion. Nature 2017, 542, 372–376.
15. Schrepfer, E.; Scorrano, L. Mitofusins, from mitochondria to metabolism. Mol. Cell. 2016, 61, 683–694.
16. Pagliuso, A.; Cossart, P.; Stavru, F. The ever-growing complexity of the mitochondrial fission machinery. Cell. Mol. Life Sci. 2017.
17. MacVicar, T.; Langer, T. Opa1 processing in cell death and disease—The long and short of it. J. Cell Sci. 2016, 129, 2297–2306.
18. Adachi, Y.; Itoh, K.; Yamada, T.; Cerveny, K.L.; Suzuki, T.L.; Macdonald, P.; Frohman, M.A.; Ramachandran, R.; Iijima, M.; Sesaki, H. Coincident phosphatidic acid interaction restrains Drp1 in mitochondrial division. Mol. Cell 2016, 63, 1034–1043.
19. Van Laar, V.S.; Berman, S.B.; Hastings, T.G. Mic60/mitofilin overexpression alters mitochondrial dynamics and attenuates vulnerability of dopaminergic cells to dopamine and rotenone. Neurobiol. Dis. 2016, 91, 247–261.
20. Schorr, S.; van der Laan, M. Integrative functions of the mitochondrial contact site and cristae organizing system. Semin. Cell Dev. Biol. 2017.
21. Wollweber, F.; von der Malsburg, K.; van der Laan, M. Mitochondrial contact site and cristae organizing system: A central player in membrane shaping and crosstalk. Biochim. Biophys. Acta 2017, 1864, 1481–1489.
22. Wang, K.; Yan, R.; Cooper, K.F.; Strich, R. Cyclin C mediates stress-induced mitochondrial fission and apoptosis. Mol. Biol. Cell 2015, 26, 1030–1043.
23. Strich, R.; Cooper, K.F. The dual role of cyclin C connects stress regulated gene expression to mitochondrial dynamics. Microb. Cell 2014, 1, 318–324.
24. Cooper, K.F.; Khakhina, S.; Kim, S.K.; Strich, R. Stress-induced nuclear-to-cytoplasmic translocation of cyclin C promotes mitochondrial fission in yeast. Dev. Cell 2014, 28, 161–173.
25. Horbay, R.; Bilyy, R. Mitochondrial dynamics during cell cycling. Apoptosis 2016, 21, 1327–1335.
26. Ramachandran, R. Mitochondrial dynamics: The dynamin superfamily and execution by collusion. Semin. Cell Dev. Biol. 2017.
27. Hu, C.; Huang, Y.; Li, L. Drp1-dependent mitochondrial fission plays critical roles in physiological and pathological progresses in mammals. Int. J. Mol. Sci. 2017, 18, 144.
28. Antonny, B.; Burd, C.; De Camilli, P.; Chen, E.; Daumke, O.; Faelber, K.; Ford, M.; Frolov, V.A.; Frost, A.; Hinshaw, J.E.; et al. Membrane fission by dynamin: What we know and what we need to know. EMBO J. 2016, 35, 2270–2284.
29. Kraus, F.; Ryan, M.T. The constriction and scission machineries involved in mitochondrial fission. J. Cell Sci. 2017, 130, 2953–2960.
30. Atkins, K.; Dasgupta, A.; Chen, K.H.; Mewburn, J.; Archer, S.L. The role of Drp1 adaptor proteins MiD49 and MiD51 in mitochondrial fission: Implications for human disease. Clin. Sci. 2016, 130, 1861–1874.
31. Osellame, L.D.; Singh, A.P.; Stroud, D.A.; Palmer, C.S.; Stojanovski, D.; Ramachandran, R.; Ryan, M.T. Cooperative and independent roles of the Drp1 adaptors Mff, MiD49 and MiD51 in mitochondrial fission. J. Cell Sci. 2016, 129, 2170–2181.
32. Liu, R.; Chan, D.C. The mitochondrial fission receptor Mff selectively recruits oligomerized Drp1. Mol. Biol. Cell 2015, 26, 4466–4477.
33. Nagdas, S.; Kashatus, D.F. The interplay between oncogenic signaling networks and mitochondrial dynamics. Antioxidants 2017, 6, 33.
34. Lee, J.E.; Westrate, L.M.; Wu, H.; Page, C.; Voeltz, G.K. Multiple dynamin family members collaborate to drive mitochondrial division. Nature 2016, 540, 139–143.
35. Liesa, M.; Shirihai, O.S. Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure. Cell Metab. 2013, 17, 491–506.
36. Bordi, M.; Nazio, F.; Campello, S. The close interconnection between mitochondrial dynamics and mitophagy in cancer. Front. Oncol. 2017, 7, 81.
37. Martinez-Carreres, L.; Nasrallah, A.; Fajas, L. Cancer: Linking powerhouses to suicidal bags. Front. Oncol. 2017, 7, 204.
38. Ciccarese, F.; Ciminale, V. Escaping death: Mitochondrial redox homeostasis in cancer cells. Front. Oncol. 2017, 7, 117.
39. Wang, Y.; Nartiss, Y.; Steipe, B.; McQuibban, G.A.; Kim, P.K. ROS-induced mitochondrial depolarization initiates park2/parkin-dependent mitochondrial degradation by autophagy. Autophagy 2012, 8, 1462–1476.
40. Pena-Blanco, A.; Garcia-Saez, A.J. Bax, Bak and beyond-mitochondrial performance in apoptosis. FEBS J. 2017.
41. Kim, H.J.; Maiti, P.; Barrientos, A. Mitochondrial ribosomes in cancer. Semin. Cancer Biol. 2017, 47, 67–81.
42. Rathore, R.; McCallum, J.E.; Varghese, E.; Florea, A.M.; Busselberg, D. Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPS). Apoptosis 2017, 22, 898–919.
43. Sahl, S.J.; Hell, S.W.; Jakobs, S. Fluorescence nanoscopy in cell biology. Nat. Rev. Mol. Cell Biol. 2017, 18, 685–701.
44. Grosse, L.; Wurm, C.A.; Bruser, C.; Neumann, D.; Jans, D.C.; Jakobs, S. Bax assembles into large ring-like structures remodeling the mitochondrial outer membrane in apoptosis. EMBO J. 2016, 35, 402–413.
45. Salvador-Gallego, R.; Mund, M.; Cosentino, K.; Schneider, J.; Unsay, J.; Schraermeyer, U.; Engelhardt, J.; Ries, J.; Garcia-Saez, A.J. Bax assembly into rings and arcs in apoptotic mitochondria is linked to membrane pores. EMBO J. 2016, 35, 389–401.
46. Kalkavan, H.; Green, D.R. Momp, cell suicide as a BCL-2 family business. Cell Death Differ. 2018, 25, 46–55.
47. Suarez-Rivero, J.M.; Villanueva-Paz, M.; de la Cruz-Ojeda, P.; de la Mata, M.; Cotan, D.; Oropesa-Avila, M.; de Lavera, I.; Alvarez-Cordoba, M.; Luzon-Hidalgo, R.; Sanchez-Alcazar, J.A. Mitochondrial dynamics in mitochondrial diseases. Diseases 2016, 5, 1.
48. Simula, L.; Nazio, F.; Campello, S. The mitochondrial dynamics in cancer and immune-surveillance. Semin. Cancer Biol. 2017, 47, 29–42.
49. Srinivasan, S.; Guha, M.; Kashina, A.; Avadhani, N.G. Mitochondrial dysfunction and mitochondrial dynamics-the cancer connection. Biochim. Biophys. Acta 2017, 1858, 602–614.
50. Trotta, A.P.; Chipuk, J.E. Mitochondrial dynamics as regulators of cancer biology. Cell. Mol. Life Sci. 2017, 74, 1999–2017.
51. Gonzalez-Franquesa, A.; Patti, M.E. Insulin resistance and mitochondrial dysfunction. Adv. Exp. Med. Biol. 2017, 982, 465–520.
52. Rovira-Llopis, S.; Banuls, C.; Diaz-Morales, N.; Hernandez-Mijares, A.; Rocha, M.; Victor, V.M. Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications. Redox Biol. 2017, 11, 637–645.
53. Wada, J.; Nakatsuka, A. Mitochondrial dynamics and mitochondrial dysfunction in diabetes. Acta Med. Okayama 2016, 70, 151–158.
54. Anzell, A.R.; Maizy, R.; Przyklenk, K.; Sanderson, T.H. Mitochondrial quality control and disease: Insights into ischemia-reperfusion injury. Mol. Neurobiol. 2017.
55. Nan, J.; Zhu, W.; Rahman, M.S.; Liu, M.; Li, D.; Su, S.; Zhang, N.; Hu, X.; Yu, H.; Gupta, M.P.; et al. Molecular regulation of mitochondrial dynamics in cardiac disease. Biochim. Biophys. Acta 2017, 1864, 1260–1273.
56. Tong, M.; Sadoshima, J. Mitochondrial autophagy in cardiomyopathy. Curr. Opin. Genet. Dev. 2016, 38, 8–15.
57. Marin-Garcia, J.; Akhmedov, A.T. Mitochondrial dynamics and cell death in heart failure. Heart Fail. Rev. 2016, 21, 123–136.
58. Vasquez-Trincado, C.; Garcia-Carvajal, I.; Pennanen, C.; Parra, V.; Hill, J.A.; Rothermel, B.A.; Lavandero, S. Mitochondrial dynamics, mitophagy and cardiovascular disease. J. Physiol. 2016, 594, 509–525.
59. Chiang, S.; Kalinowski, D.S.; Jansson, P.J.; Richardson, D.R.; Huang, M.L. Mitochondrial dysfunction in the neuro-degenerative and cardio-degenerative disease, friedreich’s ataxia. Neurochem. Int. 2017.
60. Gao, J.; Wang, L.; Liu, J.; Xie, F.; Su, B.; Wang, X. Abnormalities of mitochondrial dynamics in neurodegenerative diseases. Antioxidants 2017, 6, 25.
61. Wu, Q.; Luo, C.L.; Tao, L.Y. Dynamin-related protein 1 (Drp1) mediating mitophagy contributes to the pathophysiology of nervous system diseases and brain injury. Histol. Histopathol. 2017, 32, 551–559.
62. Bose, A.; Beal, M.F. Mitochondrial dysfunction in parkinson’s disease. J. Neurochem. 2016, 139 (Suppl. S1), 216–231.
63. Cai, Q.; Tammineni, P. Alterations in mitochondrial quality control in alzheimer’s disease. Front. Cell Neurosci. 2016, 10, 24.
64. Boengler, K.; Kosiol, M.; Mayr, M.; Schulz, R.; Rohrbach, S. Mitochondria and ageing: Role in heart, skeletal muscle and adipose tissue. J. Cachexia Sarcopenia Muscle 2017, 8, 349–369.
65. Lopez-Lluch, G. Mitochondrial activity and dynamics changes regarding metabolism in ageing and obesity. Mech. Ageing Dev. 2017, 162, 108–121.
66. Wang, W.; Gong, G.; Wang, X.; Wei-LaPierre, L.; Cheng, H.; Dirksen, R.; Sheu, S.S. Mitochondrial flash: Integrative reactive oxygen species and ph signals in cell and organelle biology. Antioxid. Redox Signal. 2016, 25, 534–549.
67. Bae, Y.S.; Oh, H.; Rhee, S.G.; Yoo, Y.D. Regulation of reactive oxygen species generation in cell signaling. Mol. Cells 2011, 32, 491–509.
68. Brand, M.D. Mitochondrial generation of superoxide and hydrogen peroxide as the source of mitochondrial redox signaling. Free Radic. Biol. Med. 2016, 100, 14–31.
69. Wong, H.S.; Dighe, P.A.; Mezera, V.; Monternier, P.A.; Brand, M.D. Production of superoxide and hydrogen peroxide from specific mitochondrial sites under different bioenergetic conditions. J. Biol. Chem. 2017, 292, 16804–16809.
70. Zou, X.; Ratti, B.A.; O’Brien, J.G.; Lautenschlager, S.O.; Gius, D.R.; Bonini, M.G.; Zhu, Y. Manganese superoxide dismutase (SOD2): Is there a center in the universe of mitochondrial redox signaling? J. Bioenerg. Biomembr. 2017, 49, 325–333.
71. Mondola, P.; Damiano, S.; Sasso, A.; Santillo, M. The Cu, Zn superoxide dismutase: Not only a dismutase enzyme. Front. Physiol. 2016, 7, 594.
72. Gao, X.; Schottker, B. Reduction-oxidation pathways involved in cancer development: A systematic review of literature reviews. Oncotarget 2017, 8, 51888–51906.
73. Scialo, F.; Fernandez-Ayala, D.J.; Sanz, A. Role of mitochondrial reverse electron transport in ros signaling: Potential roles in health and disease. Front. Physiol. 2017, 8, 428.
74. Kuksal, N.; Chalker, J.; Mailloux, R.J. Progress in understanding the molecular oxygen paradox-function of mitochondrial reactive oxygen species in cell signaling. Biol. Chem. 2017, 398, 1209–1227.
75. Roy, J.; Galano, J.M.; Durand, T.; Le Guennec, J.Y.; Lee, J.C. Physiological role of reactive oxygen species as promoters of natural defenses. FASEB J. 2017, 31, 3729–3745.
76. Sies, H.; Berndt, C.; Jones, D.P. Oxidative stress. Annu. Rev. Biochem. 2017, 86, 715–748.
77. Sies, H. Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress. Redox Biol. 2017, 11, 613–619.
78. Mahaseth, T.; Kuzminov, A. Potentiation of hydrogen peroxide toxicity: From catalase inhibition to stable DNA-iron complexes. Mutat. Res. 2017, 773, 274–281.
79. Leitao, E.F.V.; Ventura, E.; de Souza, M.A.F.; Riveros, J.M.; do Monte, S.A. Spin-forbidden branching in the mechanism of the intrinsic haber-weiss reaction. ChemistryOpen 2017, 6, 360–363.
80. Gammella, E.; Recalcati, S.; Cairo, G. Dual role of ROS as signal and stress agents: Iron tips the balance in favor of toxic effects. Oxid. Med. Cell. Longev. 2016, 2016, 8629024.
81. Little, A.C.; Sulovari, A.; Danyal, K.; Heppner, D.E.; Seward, D.J.; Van der Vliet, A. Paradoxical roles of dual oxidases in cancer biology. Free Radic. Biol. Med. 2017, 110, 117–132.
82. Zou, Z.; Chang, H.; Li, H.; Wang, S. Induction of reactive oxygen species: An emerging approach for cancer therapy. Apoptosis 2017, 22, 1321–1335.
83. Vakifahmetoglu-Norberg, H.; Ouchida, A.T.; Norberg, E. The role of mitochondria in metabolism and cell death. Biochem. Biophys. Res. Commun. 2017, 482, 426–431.
84. Rodic, S.; Vincent, M.D. Reactive oxygen species (ROS) are a key determinant of cancer’s metabolic phenotype. Int. J. Cancer 2018, 142, 440–448.
85. Idelchik, M.; Begley, U.; Begley, T.J.; Melendez, J.A. Mitochondrial ROS control of cancer. Semin. Cancer Biol. 2017, 47, 57–66.
86. Liu, J.; Wang, Z. Increased oxidative stress as a selective anticancer therapy. Oxid. Med. Cell. Longev. 2015, 2015, 294303.
87. Chen, H.; Chan, D.C. Mitochondrial dynamics in regulating the unique phenotypes of cancer and stem cells. Cell Metab. 2017, 26, 39–48.
88. Raza, M.H.; Siraj, S.; Arshad, A.; Waheed, U.; Aldakheel, F.; Alduraywish, S.; Arshad, M. ROS-modulated therapeutic approaches in cancer treatment. J. Cancer Res. Clin. Oncol. 2017.
89. Galadari, S.; Rahman, A.; Pallichankandy, S.; Thayyullathil, F. Reactive oxygen species and cancer paradox: To promote or to suppress? Free Radic. Biol. Med. 2017, 104, 144–164.
90. Milkovic, L.; Siems, W.; Siems, R.; Zarkovic, N. Oxidative stress and antioxidants in carcinogenesis and integrative therapy of cancer. Curr. Pharm. Des. 2014, 20, 6529–6542.
91. Cabello, C.M.; Bair, W.B.; 3rd; Wondrak, G.T. Experimental therapeutics: Targeting the redox achilles heel of cancer. Curr. Opin. Investig. Drugs 2007, 8, 1022–1037.
92. Marullo, R.; Werner, E.; Degtyareva, N.; Moore, B.; Altavilla, G.; Ramalingam, S.S.; Doetsch, P.W. Cisplatin induces a mitochondrial-ROS response that contributes to cytotoxicity depending on mitochondrial redox status and bioenergetic functions. PLoS ONE 2013, 8, e81162.
93. Mut-Salud, N.; Alvarez, P.J.; Garrido, J.M.; Carrasco, E.; Aranega, A.; Rodriguez-Serrano, F. Antioxidant intake and antitumor therapy: Toward nutritional recommendations for optimal results. Oxid. Med. Cell. Longev. 2016, 2016, 6719534.
94. Abo-Neima, S.E. Treatment of cancer by low intensity laser radiation therapy. Prog. Biophys. Mol. Biol. 2017.
95. Deng, K.; Li, C.; Huang, S.; Xing, B.; Jin, D.; Zeng, Q.; Hou, Z.; Lin, J. Recent progress in near infrared light triggered photodynamic therapy. Small 2017, 13.
96. Luo, H.; Chiang, H.H.; Louw, M.; Susanto, A.; Chen, D. Nutrient sensing and the oxidative stress response. Trends Endocrinol. Metab. 2017, 28, 449–460.
97. Wang, C.H.; Wu, S.B.; Wu, Y.T.; Wei, Y.H. Oxidative stress response elicited by mitochondrial dysfunction: Implication in the pathophysiology of aging. Exp. Biol. Med. 2013, 238, 450–460.
98. Yang, L.; Long, Q.; Liu, J.; Tang, H.; Li, Y.; Bao, F.; Qin, D.; Pei, D.; Liu, X. Mitochondrial fusion provides an ‘initial metabolic complementation’ controlled by mtdna. Cell. Mol. Life Sci. 2015, 72, 2585–2598.
99. Enns, G.M.; Cowan, T.M. Glutathione as a redox biomarker in mitochondrial disease-implications for therapy. J. Clin. Med. 2017, 6, 50.
100. Jiao, Y.; Wang, Y.; Guo, S.; Wang, G. Glutathione peroxidases as oncotargets. Oncotarget 2017, 8, 80093–80102.
101. Couto, N.; Wood, J.; Barber, J. The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Radic. Biol. Med. 2016, 95, 27–42.
102. Shutt, T.; Geoffrion, M.; Milne, R.; McBride, H.M. The intracellular redox state is a core determinant of mitochondrial fusion. EMBO Rep. 2012, 13, 909–915.
103. Glorieux, C.; Calderon, P.B. Catalase, a remarkable enzyme: Targeting the oldest antioxidant enzyme to find a new cancer treatment approach. Biol. Chem. 2017, 398, 1095–1108.
104. Rhee, S.G.; Kil, I.S. Multiple functions and regulation of mammalian peroxiredoxins. Annu. Rev. Biochem. 2017, 86, 749–775.
105. Zhang, J.; Li, X.; Han, X.; Liu, R.; Fang, J. Targeting the thioredoxin system for cancer therapy. Trends Pharmacol. Sci. 2017, 38, 794–808.
106. Monteiro, H.P.; Ogata, F.T.; Stern, A. Thioredoxin promotes survival signaling events under nitrosative/oxidative stress associated with cancer development. Biomed. J. 2017, 40, 189–199.
107. Cunniff, B.; Wozniak, A.N.; Sweeney, P.; DeCosta, K.; Heintz, N.H. Peroxiredoxin 3 levels regulate a mitochondrial redox setpoint in malignant mesothelioma cells. Redox Biol. 2014, 3, 79–87.
108. Baffy, G. Mitochondrial uncoupling in cancer cells: Liabilities and opportunities. Biochim. Biophys. Acta 2017, 1858, 655–664.
109. 2-activated mitochondrial phospholipase iPLA(2)gamma prevents lipotoxic oxidative stress in synergy with UCP2, amplifies signaling via G-protein-coupled receptor GPR40, and regulates insulin secretion in pancreatic beta-cells. Antioxid. Redox Signal. 2015, 23, 958–972.
110. Oh, S.E.; Mouradian, M.M. Cytoprotective mechanisms of DJ-1 against oxidative stress through modulating ERK1/2 and ASK1 signal transduction. Redox Biol. 2018, 14, 211–217.
111. Almeida, L.O.; Goto, R.N.; Neto, M.P.; Sousa, L.O.; Curti, C.; Leopoldino, A.M. Set overexpression in HEK293 cells regulates mitochondrial uncoupling proteins levels within a mitochondrial fission/reduced autophagic flux scenario. Biochem. Biophys. Res. Commun. 2015, 458, 300–306.
112. Shimizu, Y.; Lambert, J.P.; Nicholson, C.K.; Kim, J.J.; Wolfson, D.W.; Cho, H.C.; Husain, A.; Naqvi, N.; Chin, L.S.; Li, L.; et al. Dj-1 protects the heart against ischemia-reperfusion injury by regulating mitochondrial fission. J. Mol. Cell. Cardiol. 2016, 97, 56–66.
113. Benfeitas, R.; Uhlen, M.; Nielsen, J.; Mardinoglu, A. New challenges to study heterogeneity in cancer redox metabolism. Front. Cell Dev. Biol. 2017, 5, 65.
114. Moloney, J.N.; Cotter, T.G. ROS signalling in the biology of cancer. Semin. Cell Dev. Biol. 2017.
115. Basak, P.; Sadhukhan, P.; Sarkar, P.; Sil, P.C. Perspectives of the NRF-2 signaling pathway in cancer progression and therapy. Toxicol. Rep. 2017, 4, 306–318.
116. Holmstrom, K.M.; Kostov, R.V.; Dinkova-Kostova, A.T. The multifaceted role of Nrf2 in mitochondrial function. Curr. Opin. Toxicol. 2016, 1, 80–91.
117. Krajka-Kuzniak, V.; Paluszczak, J.; Baer-Dubowska, W. The NRF2-are signaling pathway: An update on its regulation and possible role in cancer prevention and treatment. Pharmacol. Rep. 2017, 69, 393–402.
118. Holmstrom, K.M.; Baird, L.; Zhang, Y.; Hargreaves, I.; Chalasani, A.; Land, J.M.; Stanyer, L.; Yamamoto, M.; Dinkova-Kostova, A.T.; Abramov, A.Y. Nrf2 impacts cellular bioenergetics by controlling substrate availability for mitochondrial respiration. Biol. Open 2013, 2, 761–770.
119. Suzuki, T.; Yamamoto, M. Stress-sensing mechanisms and the physiological roles of the keap1-Nrf2 system during cellular stress. J. Biol. Chem. 2017, 292, 16817–16824.
120. Jin, Y.N.; Yu, Y.V.; Gundemir, S.; Jo, C.; Cui, M.; Tieu, K.; Johnson, G.V. Impaired mitochondrial dynamics and Nrf2 signaling contribute to compromised responses to oxidative stress in striatal cells expressing full-length mutant huntingtin. PLoS ONE 2013, 8, e57932.
121. Negrette-Guzman, M.; Huerta-Yepez, S.; Vega, M.I.; Leon-Contreras, J.C.; Hernandez-Pando, R.; Medina-Campos, O.N.; Rodriguez, E.; Tapia, E.; Pedraza-Chaverri, J. Sulforaphane induces differential modulation of mitochondrial biogenesis and dynamics in normal cells and tumor cells. Food Chem. Toxicol. 2017, 100, 90–102.
122. Schito, L.; Semenza, G.L. Hypoxia-inducible factors: Master regulators of cancer progression. Trends Cancer 2016, 2, 758–770.
123. Masoud, G.N.; Li, W. Hif-1alpha pathway: Role, regulation and intervention for cancer therapy. Acta Pharm. Sin. B 2015, 5, 378–389.
124. Nguyen, T.L.; Duran, R.V. Prolyl hydroxylase domain enzymes and their role in cell signaling and cancer metabolism. Int. J. Biochem. Cell Biol. 2016, 80, 71–80.
125. Ivan, M.; Kaelin, W.G.; Jr. The EGLN-HIF O2-sensing system: Multiple inputs and feedbacks. Mol. Cell 2017, 66, 772–779.
126. Plecita-Hlavata, L.; Jezek, J.; Jezek, P. Aglycemia keeps mitochondrial oxidative phosphorylation under hypoxic conditions in HepG2 cells. J. Bioenerg. Biomembr. 2015, 47, 467–476.
127. Hernansanz-Agustin, P.; Izquierdo-Alvarez, A.; Sanchez-Gomez, F.J.; Ramos, E.; Villa-Pina, T.; Lamas, S.; Bogdanova, A.; Martinez-Ruiz, A. Acute hypoxia produces a superoxide burst in cells. Free Radic. Biol. Med. 2014, 71, 146–156.
128. Smith, K.A.; Waypa, G.B.; Schumacker, P.T. Redox signaling during hypoxia in mammalian cells. Redox Biol. 2017, 13, 228–234.
129. Fernandez-Aguera, M.C.; Gao, L.; Gonzalez-Rodriguez, P.; Pintado, C.O.; Arias-Mayenco, I.; Garcia-Flores, P.; Garcia-Perganeda, A.; Pascual, A.; Ortega-Saenz, P.; Lopez-Barneo, J. Oxygen sensing by arterial chemoreceptors depends on mitochondrial complex I signaling. Cell Metab. 2015, 22, 825–837.
130. Guzy, R.D.; Schumacker, P.T. Oxygen sensing by mitochondria at complex III: The paradox of increased reactive oxygen species during hypoxia. Exp. Physiol. 2006, 91, 807–819.
131. Chandel, N.S. Mitochondrial regulation of oxygen sensing. Adv. Exp. Med. Biol. 2010, 661, 339–354.
132. Han, X.J.; Yang, Z.J.; Jiang, L.P.; Wei, Y.F.; Liao, M.F.; Qian, Y.; Li, Y.; Huang, X.; Wang, J.B.; Xin, H.B.; et al. Mitochondrial dynamics regulates hypoxia-induced migration and antineoplastic activity of cisplatin in breast cancer cells. Int. J. Oncol. 2015, 46, 691–700.
133. Wan, Y.Y.; Zhang, J.F.; Yang, Z.J.; Jiang, L.P.; Wei, Y.F.; Lai, Q.N.; Wang, J.B.; Xin, H.B.; Han, X.J. Involvement of Drp1 in hypoxia-induced migration of human glioblastoma u251 cells. Oncol. Rep. 2014, 32, 619–626.
134. Salminen, A.; Kaarniranta, K.; Kauppinen, A. AMPK and HIF signaling pathways regulate both longevity and cancer growth: The good news and the bad news about survival mechanisms. Biogerontology 2016, 17, 655–680.
135. Dier, U.; Shin, D.H.; Hemachandra, L.P.; Uusitalo, L.M.; Hempel, N. Bioenergetic analysis of ovarian cancer cell lines: Profiling of histological subtypes and identification of a mitochondria-defective cell line. PLoS ONE 2014, 9, e98479.
136. Ryuno, H.; Naguro, I.; Kamiyama, M. ASK family and cancer. Adv. Biol. Regul. 2017, 66, 72–84.
137. Latimer, H.R.; Veal, E.A. Peroxiredoxins in regulation of MAPK signalling pathways; sensors and barriers to signal transduction. Mol. Cells 2016, 39, 40–45.
138. Lu, J.; Holmgren, A. Thioredoxin system in cell death progression. Antioxid. Redox Signal. 2012, 17, 1738–1747.
139. Matsuzawa, A. Thioredoxin and redox signaling: Roles of the thioredoxin system in control of cell fate. Arch Biochem. Biophys. 2017, 617, 101–105.
140. Kim, H.; Scimia, M.C.; Wilkinson, D.; Trelles, R.D.; Wood, M.R.; Bowtell, D.; Dillin, A.; Mercola, M.; Ronai, Z.A. Fine-tuning of Drp1/Fis1 availability by akap121/siah2 regulates mitochondrial adaptation to hypoxia. Mol. Cell 2011, 44, 532–544.
141. Tormos, A.M.; Talens-Visconti, R.; Nebreda, A.R.; Sastre, J. P38 MAPK: A dual role in hepatocyte proliferation through reactive oxygen species. Free Radic. Res. 2013, 47, 905–916.
142. Nakayama, K.; Qi, J.; Ronai, Z. The ubiquitin ligase siah2 and the hypoxia response. Mol. Cancer Res. 2009, 7, 443–451.
143. Ko, S.H.; Choi, G.E.; Oh, J.Y.; Lee, H.J.; Kim, J.S.; Chae, C.W.; Choi, D.; Han, H.J. Succinate promotes stem cell migration through the gpr91-dependent regulation of Drp1-mediated mitochondrial fission. Sci. Rep. 2017, 7, 12582.
144. Zhang, X.M.; Zhang, L.; Wang, G.; Niu, W.; He, Z.; Ding, L.; Jia, J. Suppression of mitochondrial fission in experimental cerebral ischemia: The potential neuroprotective target of p38 MAPK inhibition. Neurochem. Int. 2015, 90, 1–8.
145. Obsil, T.; Obsilova, V. Structural aspects of protein kinase ASK1 regulation. Adv. Biol. Regul. 2017, 66, 31–36.
146. Dhanasekaran, D.N.; Reddy, E.P. JNK signaling in apoptosis. Oncogene 2008, 27, 6245–6251.
147. Ferro, E.; Goitre, L.; Baldini, E.; Retta, S.F.; Trabalzini, L. Ras gtpases are both regulators and effectors of redox agents. Methods Mol. Biol. 2014, 1120, 55–74.
148. Papke, B.; Der, C.J. Drugging Ras: Know the enemy. Science 2017, 355, 1158–1163.
149. Simanshu, D.K.; Nissley, D.V.; McCormick, F. Ras proteins and their regulators in human disease. Cell 2017, 170, 17–33.
150. Schopel, M.; Potheraveedu, V.N.; Al-Harthy, T.; Abdel-Jalil, R.; Heumann, R.; Stoll, R. The small gtpases ras and rheb studied by multidimensional nmr spectroscopy: Structure and function. Biol. Chem. 2017, 398, 577–588.
151. Tanimura, S.; Takeda, K. ERK signalling as a regulator of cell motility. J. Biochem. 2017, 162, 145–154.
152. Mitchell, L.; Hobbs, G.A.; Aghajanian, A.; Campbell, S.L. Redox regulation of Ras and Rho GTPases: Mechanism and function. Antioxid. Redox Signal. 2013, 18, 250–258.
153. Cook, S.J.; Stuart, K.; Gilley, R.; Sale, M.J. Control of cell death and mitochondrial fission by ERK1/2 map kinase signalling. FEBS J. 2017, 284, 4177–4195.
154. Kashatus, J.A.; Nascimento, A.; Myers, L.J.; Sher, A.; Byrne, F.L.; Hoehn, K.L.; Counter, C.M.; Kashatus, D.F. ERK2 phosphorylation of Drp1 promotes mitochondrial fission and MAPK-driven tumor growth. Mol. Cell 2015, 57, 537–551.
155. Serasinghe, M.N.; Wieder, S.Y.; Renault, T.T.; Elkholi, R.; Asciolla, J.J.; Yao, J.L.; Jabado, O.; Hoehn, K.; Kageyama, Y.; Sesaki, H.; et al. Mitochondrial division is requisite to ras-induced transformation and targeted by oncogenic MAPK pathway inhibitors. Mol. Cell 2015, 57, 521–536.
156. Taguchi, N.; Ishihara, N.; Jofuku, A.; Oka, T.; Mihara, K. Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission. J. Biol. Chem. 2007, 282, 11521–11529.
157. Colomer, C.; Marruecos, L.; Vert, A.; Bigas, A.; Espinosa, L. Nf-kappab members left home: Nf-kappab-independent roles in cancer. Biomedicines 2017, 5, 26.
158. Darvishi, B.; Farahmand, L.; Eslami, S.Z.; Majidzadeh, A.K. Nf-kappab as the main node of resistance to receptor tyrosine kinase inhibitors in triple-negative breast cancer. Tumour Biol. 2017, 39.
159. Begalli, F.; Bennett, J.; Capece, D.; Verzella, D.; D’Andrea, D.; Tornatore, L.; Franzoso, G. Unlocking the nf-kappab conundrum: Embracing complexity to achieve specificity. Biomedicines 2017, 5, 50.
160. Capece, D.; Verzella, D.; Tessitore, A.; Alesse, E.; Capalbo, C.; Zazzeroni, F. Cancer secretome and inflammation: The bright and the dark sides of NF-μB. Semin. Cell. Dev. Biol. 2017.
161. Laforge, M.; Rodrigues, V.; Silvestre, R.; Gautier, C.; Weil, R.; Corti, O.; Estaquier, J. Nf-kappab pathway controls mitochondrial dynamics. Cell Death Differ. 2016, 23, 89–98.
162. Mitchell, S.; Vargas, J.; Hoffmann, A. Signaling via the NF-μB system. Wiley Interdiscip. Rev. Syst. Biol. Med. 2016, 8, 227–241.
163. Buelna-Chontal, M.; Zazueta, C. Redox activation of Nrf2 & NF-μB: A double end sword? Cell Signal. 2013, 25, 2548–2557.
164. Busquets-Cortes, C.; Capo, X.; Martorell, M.; Tur, J.A.; Sureda, A.; Pons, A. Training and acute exercise modulates mitochondrial dynamics in football players’ blood mononuclear cells. Eur. J. Appl. Physiol. 2017, 117, 1977–1987.
165. Uzhachenko, R.; Ivanov, S.V.; Yarbrough, W.G.; Shanker, A.; Medzhitov, R.; Ivanova, A.V. Fus1/Tusc2 is a novel regulator of mitochondrial calcium handling, Ca2+-coupled mitochondrial processes, and Ca2+-dependent NFAT and NF-μB pathways in CD4+ T cells. Antioxid. Redox Signal. 2014, 20, 1533–1547.
166. Aravamudan, B.; Kiel, A.; Freeman, M.; Delmotte, P.; Thompson, M.; Vassallo, R.; Sieck, G.C.; Pabelick, C.M.; Prakash, Y.S. Cigarette smoke-induced mitochondrial fragmentation and dysfunction in human airway smooth muscle. Am. J. Physiol. Lung Cell. Mol. Physiol. 2014, 306, L840–L854.
167. Cordero, M.D. AMP-Activated Protein Kinase; Springer: Berlin/Heidelberg, Germany; New York, NY, USA, 2016.
168. Herzig, S.; Shaw, R.J. AMPK: Guardian of metabolism and mitochondrial homeostasis. Nat. Rev. Mol. Cell Biol. 2017.
169. Carling, D. AMPK signalling in health and disease. Curr. Opin. Cell Biol. 2017, 45, 31–37.
170. Garcia, D.; Shaw, R.J. AMPK: Mechanisms of cellular energy sensing and restoration of metabolic balance. Mol. Cell 2017, 66, 789–800.
171. Hardie, D.G.; Lin, S.C. AMP-activated protein kinase—Not just an energy sensor. F1000Research 2017, 6, 1724.
172. Ross, F.A.; MacKintosh, C.; Hardie, D.G. AMP-activated protein kinase: A cellular energy sensor that comes in 12 flavours. FEBS J. 2016, 283, 2987–3001.
173. He, X.; Li, C.; Ke, R.; Luo, L.; Huang, D. Down-regulation of adenosine monophosphate-activated protein kinase activity: A driver of cancer. Tumour Biol. 2017, 39.
174. Jeon, S.M.; Hay, N. The double-edged sword of AMPK signaling in cancer and its therapeutic implications. Arch. Pharm. Res. 2015, 38, 346–357.
175. Faubert, B.; Vincent, E.E.; Poffenberger, M.C.; Jones, R.G. The amp-activated protein kinase (AMPK) and cancer: Many faces of a metabolic regulator. Cancer Lett. 2015, 356, 165–170.
176. Zmijewski, J.W.; Banerjee, S.; Bae, H.; Friggeri, A.; Lazarowski, E.R.; Abraham, E. Exposure to hydrogen peroxide induces oxidation and activation of amp-activated protein kinase. J. Biol. Chem. 2010, 285, 33154–33164.
177. Rabinovitch, R.C.; Samborska, B.; Faubert, B.; Ma, E.H.; Gravel, S.P.; Andrzejewski, S.; Raissi, T.C.; Pause, A.; St-Pierre, J.; Jones, R.G. AMPK maintains cellular metabolic homeostasis through regulation of mitochondrial reactive oxygen species. Cell Rep. 2017, 21, 1–9.
178. Han, Y.; Wang, Q.; Song, P.; Zhu, Y.; Zou, M.H. Redox regulation of the amp-activated protein kinase. PLoS ONE 2010, 5, e15420.
179. Shao, D.; Oka, S.; Liu, T.; Zhai, P.; Ago, T.; Sciarretta, S.; Li, H.; Sadoshima, J. A redox-dependent mechanism for regulation of AMPK activation by thioredoxin1 during energy starvation. Cell Metab. 2014, 19, 232–245.
180. Auciello, F.R.; Ross, F.A.; Ikematsu, N.; Hardie, D.G. Oxidative stress activates AMPK in cultured cells primarily by increasing cellular amp and/or adp. FEBS Lett. 2014, 588, 3361–3366.
181. Wu, S.B.; Wu, Y.T.; Wu, T.P.; Wei, Y.H. Role of ampk-mediated adaptive responses in human cells with mitochondrial dysfunction to oxidative stress. Biochim. Biophys. Acta 2014, 1840, 1331–1344.
182. Cheng, J.; Zhang, T.; Ji, H.; Tao, K.; Guo, J.; Wei, W. Functional characterization of amp-activated protein kinase signaling in tumorigenesis. Biochim. Biophys. Acta 2016, 1866, 232–251.
183. Kang, S.W.; Haydar, G.; Taniane, C.; Farrell, G.; Arias, I.M.; Lippincott-Schwartz, J.; Fu, D. AMPK activation prevents and reverses drug-induced mitochondrial and hepatocyte injury by promoting mitochondrial fusion and function. PLoS ONE 2016, 11, e0165638.
184. Toyama, E.Q.; Herzig, S.; Courchet, J.; Lewis, T.L.; Jr.; Loson, O.C.; Hellberg, K.; Young, N.P.; Chen, H.; Polleux, F.; Chan, D.C.; et al. Metabolism. AMP-activated protein kinase mediates mitochondrial fission in response to energy stress. Science 2016, 351, 275–281.
185. Georgakopoulos, N.D.; Wells, G.; Campanella, M. The pharmacological regulation of cellular mitophagy. Nat. Chem. Biol. 2017, 13, 136–146.
186. Senft, D.; Ronai, Z.A. Regulators of mitochondrial dynamics in cancer. Curr. Opin. Cell Biol. 2016, 39, 43–52.
187. Escobar-Henriques, M.; Anton, F. Mechanistic perspective of mitochondrial fusion: Tubulation vs. Fragmentation. Biochim. Biophys. Acta 2013, 1833, 162–175.
188. Xie, Q.; Wu, Q.; Horbinski, C.M.; Flavahan, W.A.; Yang, K.; Zhou, W.; Dombrowski, S.M.; Huang, Z.; Fang, X.; Shi, Y.; et al. Mitochondrial control by Drp1 in brain tumor initiating cells. Nat. Neurosci. 2015, 18, 501–510.
189. Von Eyss, B.; Jaenicke, L.A.; Kortlever, R.M.; Royla, N.; Wiese, K.E.; Letschert, S.; McDuffus, L.A.; Sauer, M.; Rosenwald, A.; Evan, G.I.; et al. A MYC-driven change in mitochondrial dynamics limits YAP/TAZ function in mammary epithelial cells and breast cancer. Cancer Cell 2015, 28, 743–757.
190. Panciera, T.; Azzolin, L.; Cordenonsi, M.; Piccolo, S. Mechanobiology of YAP and TAZ in physiology and disease. Nat. Rev. Mol. Cell Biol. 2017, 18, 758–770.
191. Kim, M.H.; Kim, J. Role of YAP/TAZ transcriptional regulators in resistance to anti-cancer therapies. Cell. Mol. Life Sci. 2017, 74, 1457–1474.
192. Donner, A.J.; Szostek, S.; Hoover, J.M.; Espinosa, J.M. CDK8 is a stimulus-specific positive coregulator of p53 target genes. Mol. Cell 2007, 27, 121–133.
193. Khakhina, S.; Cooper, K.F.; Strich, R. Med13p prevents mitochondrial fission and programmed cell death in yeast through nuclear retention of cyclin C. Mol. Biol. Cell 2014, 25, 2807–2816.
194. Stieg, D.C.; Willis, S.D.; Ganesan, V.; Ong, K.L.; Scurozo, J.; Song, M.; Grose, J.; Strich, R.; Cooper, K.F. A complex molecular switch directs stress-induced cyclin C nuclear release through SCF (Grr1) mediated degradation of Med13. Mol. Biol. Cell 2017.
195. Li, N.; Fassl, A.; Chick, J.; Inuzuka, H.; Li, X.; Mansour, M.R.; Liu, L.; Wang, H.; King, B.; Shaik, S.; et al. Cyclin C is a haploinsufficient tumour suppressor. Nat. Cell Biol. 2014, 16, 1080–1091.
196. Ohata, N.; Ito, S.; Yoshida, A.; Kunisada, T.; Numoto, K.; Jitsumori, Y.; Kanzaki, H.; Ozaki, T.; Shimizu, K.; Ouchida, M. Highly frequent allelic loss of chromosome 6q16-23 in osteosarcoma: Involvement of cyclin C in osteosarcoma. Int. J. Mol. Med. 2006, 18, 1153–1158.
197. Wreesmann, V.B.; Ghossein, R.A.; Patel, S.G.; Harris, C.P.; Schnaser, E.A.; Shaha, A.R.; Tuttle, R.M.; Shah, J.P.; Rao, P.H.; Singh, B. Genome-wide appraisal of thyroid cancer progression. Am. J. Pathol. 2002, 161, 1549–1556.
198. Hafsi, H.; Hainaut, P. Redox control and interplay between p53 isoforms: Roles in the regulation of basal p53 levels, cell fate, and senescence. Antioxid. Redox Signal. 2011, 15, 1655–1667.
199. Yao, S.; Fan, L.Y.; Lam, E.W. The FOXO3-FOXM1 axis: A key cancer drug target and a modulator of cancer drug resistance. Semin. Cancer Biol. 2017.
200. Klotz, L.O.; Sanchez-Ramos, C.; Prieto-Arroyo, I.; Urbanek, P.; Steinbrenner, H.; Monsalve, M. Redox regulation of foxo transcription factors. Redox Biol. 2015, 6, 51–72.
201. Caliceti, C.; Nigro, P.; Rizzo, P.; Ferrari, R. ROS, Notch, and Wnt signaling pathways: Crosstalk between three major regulators of cardiovascular biology. BioMed Res. Int. 2014, 2014, 318714.
202. Verrastro, I.; Tveen-Jensen, K.; Woscholski, R.; Spickett, C.M.; Pitt, A.R. Reversible oxidation of phosphatase and tensin homolog (PTEN) alters its interactions with signaling and regulatory proteins. Free Radic. Biol. Med. 2016, 90, 24–34.
203. Laev, S.S.; Salakhutdinov, N.F.; Lavrik, O.I. Inhibitors of nuclease and redox activity of apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1). Bioorg. Med. Chem. 2017, 25, 2531–2544.
204. Tang, S.; Hou, Y.; Zhang, H.; Tu, G.; Yang, L.; Sun, Y.; Lang, L.; Tang, X.; Du, Y.E.; Zhou, M.; et al. Oxidized ATM promotes abnormal proliferation of breast CAFs through maintaining intracellular redox homeostasis and activating the PI3K-AKT, MEK-ERK, and wnt-beta-catenin signaling pathways. Cell Cycle 2015, 14, 1908–1924.
205. Espinosa-Diez, C.; Miguel, V.; Mennerich, D.; Kietzmann, T.; Sanchez-Perez, P.; Cadenas, S.; Lamas, S. Antioxidant responses and cellular adjustments to oxidative stress. Redox Biol. 2015, 6, 183–197.
206. Marinho, H.S.; Real, C.; Cyrne, L.; Soares, H.; Antunes, F. Hydrogen peroxide sensing, signaling and regulation of transcription factors. Redox Biol. 2014, 2, 535–562.
207. Kim, B.; Song, Y.S. Mitochondrial dynamics altered by oxidative stress in cancer. Free Radic. Res. 2016, 50, 1065–1070.
208. Huang, Q.; Zhan, L.; Cao, H.; Li, J.; Lyu, Y.; Guo, X.; Zhang, J.; Ji, L.; Ren, T.; An, J.; et al. Increased mitochondrial fission promotes autophagy and hepatocellular carcinoma cell survival through the ROS-modulated coordinated regulation of the NFKB and TP53 pathways. Autophagy 2016, 12, 999–1014.
209. Guido, C.; Whitaker-Menezes, D.; Lin, Z.; Pestell, R.G.; Howell, A.; Zimmers, T.A.; Casimiro, M.C.; Aquila, S.; Ando, S.; Martinez-Outschoorn, U.E.; et al. Mitochondrial fission induces glycolytic reprogramming in cancer-associated myofibroblasts, driving stromal lactate production, and early tumor growth. Oncotarget 2012, 3, 798–810.
210. Jung, J.U.; Ravi, S.; Lee, D.W.; McFadden, K.; Kamradt, M.L.; Toussaint, L.G.; Sitcheran, R. NIK/MAP3k14 regulates mitochondrial dynamics and trafficking to promote cell invasion. Curr. Biol. 2016, 26, 3288–3302.
211. Prieto, J.; Torres, J. Mitochondrial dynamics: In cell reprogramming as it is in cancer. Stem Cells Int. 2017, 2017, 8073721.
212. Son, M.J.; Kwon, Y.; Son, M.Y.; Seol, B.; Choi, H.S.; Ryu, S.W.; Choi, C.; Cho, Y.S. Mitofusins deficiency elicits mitochondrial metabolic reprogramming to pluripotency. Cell Death Differ. 2015, 22, 1957–1969.
213. Khacho, M.; Clark, A.; Svoboda, D.S.; Azzi, J.; MacLaurin, J.G.; Meghaizel, C.; Sesaki, H.; Lagace, D.C.; Germain, M.; Harper, M.E.; et al. Mitochondrial dynamics impacts stem cell identity and fate decisions by regulating a nuclear transcriptional program. Cell Stem Cell 2016, 19, 232–247.
214. Yu, T.; Sheu, S.S.; Robotham, J.L.; Yoon, Y. Mitochondrial fission mediates high glucose-induced cell death through elevated production of reactive oxygen species. Cardiovasc. Res. 2008, 79, 341–351.
215. Sedlic, F.; Muravyeva, M.Y.; Sepac, A.; Sedlic, M.; Williams, A.M.; Yang, M.; Bai, X.; Bosnjak, Z.J. Targeted modification of mitochondrial ros production converts high glucose-induced cytotoxicity to cytoprotection: Effects on anesthetic preconditioning. J. Cell. Physiol. 2017, 232, 216–224.
216. Zhang, L.; Ji, L.; Tang, X.; Chen, X.; Li, Z.; Mi, X.; Yang, L. Inhibition to Drp1 translocation can mitigate p38 MAPK-signaling pathway activation in gmc induced by hyperglycemia. Ren. Fail. 2015, 37, 903–910.
217. Kumar, S.; Pan, C.C.; Shah, N.; Wheeler, S.E.; Hoyt, K.R.; Hempel, N.; Mythreye, K.; Lee, N.Y. Activation of Mitofusin2 by Smad2-RIN1 complex during mitochondrial fusion. Mol. Cell 2016, 62, 520–531.
218. Zhang, L.; Gan, X.; He, Y.; Zhu, Z.; Zhu, J.; Yu, H. Drp1-dependent mitochondrial fission mediates osteogenic dysfunction in inflammation through elevated production of reactive oxygen species. PLoS ONE 2017, 12, e0175262.
219. Roth, D.; Krammer, P.H.; Gulow, K. Dynamin related protein 1-dependent mitochondrial fission regulates oxidative signalling in t cells. FEBS Lett. 2014, 588, 1749–1754.
220. Park, J.; Min, J.S.; Chae, U.; Lee, J.Y.; Song, K.S.; Lee, H.S.; Lee, H.J.; Lee, S.R.; Lee, D.S. Anti-inflammatory effect of oleuropein on microglia through regulation of Drp1-dependent mitochondrial fission. J. Neuroimmunol. 2017, 306, 46–52.
221. Alam, M.M.; Sohoni, S.; Kalainayakan, S.P.; Garrossian, M.; Zhang, L. Cyclopamine tartrate, an inhibitor of hedgehog signaling, strongly interferes with mitochondrial function and suppresses aerobic respiration in lung cancer cells. BMC Cancer 2016, 16, 150.
222. Shen, K.; Lu, F.; Xie, J.; Wu, M.; Cai, B.; Liu, Y.; Zhang, H.; Tan, H.; Pan, Y.; Xu, H. Cambogin exerts anti-proliferative and pro-apoptotic effects on breast adenocarcinoma through the induction of nadph oxidase 1 and the alteration of mitochondrial morphology and dynamics. Oncotarget 2016, 7, 50596–50611.
223. Guo, C.; Wang, J.; Jing, L.; Ma, R.; Liu, X.; Gao, L.; Cao, L.; Duan, J.; Zhou, X.; Li, Y.; et al. Mitochondrial dysfunction, perturbations of mitochondrial dynamics and biogenesis involved in endothelial injury induced by silica nanoparticles. Environ. Pollut. 2017.
224. Zhang, B.; Davidson, M.M.; Zhou, H.; Wang, C.; Walker, W.F.; Hei, T.K. Cytoplasmic irradiation results in mitochondrial dysfunction and Drp1-dependent mitochondrial fission. Cancer Res. 2013, 73, 6700–6710.
225. Keck, F.; Brooks-Faulconer, T.; Lark, T.; Ravishankar, P.; Bailey, C.; Salvador-Morales, C.; Narayanan, A. Altered mitochondrial dynamics as a consequence of venezuelan equine encephalitis virus infection. Virulence 2017, 1–18.
226. Michaeloudes, C.; Bhavsar, P.K.; Mumby, S.; Chung, K.F.; Adcock, I.M. Dealing with stress: Defective metabolic adaptation in chronic obstructive pulmonary disease pathogenesis. Ann. Am. Thorac. Soc. 2017, 14, S374–S382.
227. Galloway, C.A.; Yoon, Y. Perspectives on: SGP symposium on mitochondrial physiology and medicine: What comes first, misshape or dysfunction? The view from metabolic excess. J. Gen. Physiol. 2012, 139, 455–463.
228. Rosdah, A.A.; Holien, J.H.; Delbridge, L.M.; Dusting, G.J.; Lim, S.Y. Mitochondrial fission—A drug target for cytoprotection or cytodestruction? Pharmacol. Res. Perspect. 2016, 4, e00235.