👤 A. Orosz

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3
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3
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Also published as: D. E. Orosz, DE Orosz
articles
C. Crivelli, S. Garcia-Madrona, M. Gil-Minguez +428 more · 2024 · Frontiers in Neuroscience · Frontiers · added 2026-04-20
C. Crivelli, S. Garcia-Madrona, M. Gil-Minguez, R. Lujan, A. Almeida, S. Moncada, J. P. Bolanos, C. Angebault, J. Fauconnier, S. Patergnani, J. Rieusset, A. Danese, C. A. Affortit, A. Ardalan, S. Sowlati-Hashjin, H. Oduwoye, S. O. Uwumarenogie, M. Karttunen, M. D. Smith, A. Atlante, G. Amadoro, V. Latina, D. Valenti, M. Belanger, I. Allaman, P. J. Magistretti, K. F. Bell, B. Al-Mubarak, J. H. Fowler, P. S. Baxter, K. Gupta, T. Tsujita, A. M. Bertholet, A. M. Natale, P. Bisignano, J. Suzuki, A. Fedorenko, J. Hamilton, C. Bienboire-Frosini, D. Wang, M. Marcet-Rius, D. Villanueva-Garcia, A. Gazzano, A. Dominguez-Oliva, M. Bienengraeber, K. S. Echtay, M. Klingenberg, C. Bionda, J. Portoukalian, D. Schmitt, C. Rodriguez-Lafrasse, D. Ardail, M. Bozluolcay, G. Andican, S. Firtina, G. Erkol, D. Konukoglu, R. D. Burgoyne, D. A. Butterfield, B. Halliwell, M. Cater, S. M. Holter, K. A. Chamberlain, N. Huang, Y. Xie, F. LiCausi, S. Li, Y. Li, S. L. Chan, D. Liu, G. A. Kyriazis, P. Bagsiyao, X. Ouyang, M. P. Mattson, W. Chen, J. Yang, S. Chen, H. Xiang, H. Liu, D. Lin, Z. Chen, C. Zhong, I. Cho, G. J. Hwang, J. H. Cho, H. O. Song, H. E. Ji, S. Yang, A. C. Chu, P. W. Ho, K. H. Kwok, J. W. Ho, K. H. Chan, H. F. Liu, E. H. Corder, A. M. Saunders, W. J. Strittmatter, D. E. Schmechel, P. C. Gaskell, G. W. Small, S. M. Crivelli, Z. Quadri, H. J. Vekaria, Z. Zhu, P. Tripathi, A. Elsherbini, J. Cummings, Y. Zhou, G. Lee, K. Zhong, J. Fonseca, F. Cheng, C. H. Davis, K. Y. Kim, E. A. Bushong, E. A. Mills, D. Boassa, T. Shih, S. M. de la Monte, J. R. Wands, L. E. de Vries, A. Jongejan, J. Monteiro Fortes, R. Balesar, A. J. M. Rozemuller, P. D. Moerland, G. A. Dienel, D. L. Rothman, R. Domingues, C. Pereira, M. T. Cruz, A. Silva, R. Dringen, J. M. Gutterer, J. Hirrlinger, H. H. Hoepken, T. Minich, C. Ruedig, A. Lajtha, G. E. Gibson, R. H. Du, F. F. Wu, M. Lu, X. D. Shu, J. H. Ding, G. Wu, E. Winkler, J. Fortea, J. Pegueroles, D. Alcolea, O. Belbin, O. Dols-Icardo, L. Vaque-Alcazar, P. Garcia-Nogales, K. D. Garlid, M. Jaburek, P. Jezek, D. E. Orosz, M. Modriansky, S. Vassanelli, K. N. Green, H. Khashwji, T. Estrada, F. M. LaFerla, J. Grundlingh, P. I. Dargan, M. El-Zanfaly, D. M. Wood, A. Gustavsson, N. Norton, T. Fast, L. Frolich, J. Georges, D. Holzapfel, J. N. Guzman, J. Sanchez-Padilla, D. Wokosin, J. Kondapalli, E. Ilijic, P. T. Schumacker, A. Habas, J. Hahn, X. Wang, M. Margeta, P. Hanak, K. Hayakawa, E. Esposito, Y. Terasaki, Y. Liu, C. Xing, A. Herrero-Mendez, E. Fernandez, C. Maestre, D. H. So, Z. H. Tse, H. M. Tse, D. C. Yiu, W. Y. Zhang, T. Hoang, M. Kuljanin, M. Jelokhani-Niaraki, K. A. Hogan, C. C. S. Chini, E. N. Chini, N. Hu, Y. Fu, W. F. Li, X. R. Yang, M. Cao, F. F. Li, S. G. Huang, M. O. Isei, M. Crockett, E. Chen, J. Rodwell-Bullock, T. Caroll, P. A. Girardi, M. V. Ivanova, F. R. McSorley, G. Krnac, H. T. Jacobs, D. Jiang, H. Lu, D. Jimenez-Blasco, P. Santofimia-Castano, A. Gonzalez, Y. Jing, Y. Niu, C. Liu, K. Zen, D. Li, J. M. Johnson, A. D. Peterlin, E. Balderas, E. G. Sustarsic, J. A. Maschek, M. J. Lang, S. M. Joksimovic, P. Eggan, Y. Izumi, S. L. Joksimovic, V. Tesic, R. M. Dietz, S. M. Ghodsi, J. A. Heinsbroek, J. E. Orfila, N. Busquet, B. Kaltschmidt, M. Uherek, B. Volk, P. A. Baeuerle, C. Kaltschmidt, Y. Kang, L. Chen, D. Kapogiannis, K. I. Avgerinos, B. M. Kenwood, J. L. Weaver, A. Bajwa, I. K. Poon, F. L. Byrne, B. A. Murrow, E. Klotzsch, A. Smorodchenko, L. Lofler, R. Moldzio, E. Parkinson, G. J. Schutz, N. Kyrtata, H. C. A. Emsley, O. Sparasci, L. M. Parkes, B. R. Dickie, Y. Lee, B. M. Morrison, S. Lengacher, M. H. Farah, P. N. Hoffman, S. A. Liddelow, K. A. Guttenplan, L. E. Clarke, F. C. Bennett, C. J. Bohlen, L. Schirmer, N. C. de Souza-Pinto, J. R. Slevin, R. P. Wersto, M. Zhan, J. Y. Chatton, M. Manczak, M. J. Calkins, P. H. Reddy, W. Mao, X. X. Yu, A. Zhong, W. Li, J. Brush, S. W. Sherwood, A. Montesanto, P. Crocco, M. Anfossi, N. Smirne, G. Puccio, R. Colao, S. Moriguchi, N. Shioda, Y. Yamamoto, H. Tagashira, K. Fukunaga, H. Morton, S. Kshirsagar, E. Orlov, L. E. Bunquin, N. Sawant, L. Boleng, L. Mosconi, R. D. Andrews, D. C. Matthews, T. Y. Nakamura, S. Nakao, S. Wakabayashi, K. F. Neumann, L. Rojo, L. P. Navarrete, G. Farias, P. Reyes, R. B. Maccioni, D. G. Nicholls, S. Oddo, A. Caccamo, J. D. Shepherd, M. P. Murphy, T. E. Golde, R. Kayed, D. M. A. Oliver, W. R. Pearson, L. Pellerin, A. K. Bouzier-Sore, A. Aubert, S. Serres, M. Merle, R. Costalat, H. Perreten Lambert, M. Zenger, G. Azarias, R. J. Perry, D. Zhang, X. M. Zhang, J. L. Boyer, G. I. Shulman, C. Petersen, M. D. Nielsen, E. S. Andersen, A. L. Basse, M. S. Isidor, L. K. Markussen, T. Philips, J. D. Rothstein, C. Poetschke, J. Duda, J. Benkert, E. Dragicevic, T. P. Snutch, J. Striessnig, J. A. Pradeepkiran, R. A. Rice, N. C. Berchtold, C. W. Cotman, N. Rosenberg, M. Reva, F. Binda, L. Restivo, P. Depierre, J. Puyal, J. J. Ruprecht, E. R. S. Kunji, A. S. Saab, I. D. Tzvetanova, K. A. Nave, I. D. Tzvetavona, A. Trevisiol, S. Baltan, P. Dibaj, K. Kusch, A. Serrano-Pozo, Z. Li, A. Noori, H. N. Nguyen, A. Mezlini, L. Li, M. Sheridan, B. Ogretmen, C. Simons, N. Deuter, O. Pongs, T. Schneider, A. Rupprecht, I. Sarilova, O. Ninnemann, A. U. Brauer, K. Franke, G. E. Stutzmann, I. Smith, I. Parker, R. H. Swerdlow, R. Thangavel, D. Kempuraj, S. Zaheer, S. Raikwar, M. E. Ahmed, G. P. Selvakumar, B. Vaccari-Cardoso, M. Antipina, A. G. Teschemacher, S. Kasparov, B. R. Villa, A. G. George, T. E. Shutt, P. G. Sullivan, J. M. Rho, G. C. Teskey, A. A. Willette, B. B. Bendlin, E. J. Starks, A. C. Birdsill, S. C. Johnson, B. T. Christian, S. Q. Xu, X. D. Yang, Y. W. Qian, Q. Xiao Show less
The brain’s high demand for energy necessitates tightly regulated metabolic pathways to sustain physiological activity. Glucose, the primary energy substrate, undergoes complex metabolic transformatio Show more
The brain’s high demand for energy necessitates tightly regulated metabolic pathways to sustain physiological activity. Glucose, the primary energy substrate, undergoes complex metabolic transformations, with mitochondria playing a central role in ATP production via oxidative phosphorylation. Dysregulation of this metabolic interplay is implicated in Alzheimer’s disease (AD), where compromised glucose metabolism, oxidative stress, and mitochondrial dysfunction contribute to disease progression. This review explores the intricate bioenergetic crosstalk between astrocytes and neurons, highlighting the function of mitochondrial uncoupling proteins (UCPs), particularly UCP4, as important regulators of brain metabolism and neuronal function. Predominantly expressed in the brain, UCP4 reduces the membrane potential in the inner mitochondrial membrane, thereby potentially decreasing the generation of reactive oxygen species. Furthermore, UCP4 mitigates mitochondrial calcium overload and sustains cellular ATP levels through a metabolic shift from mitochondrial respiration to glycolysis. Interestingly, the levels of the neuronal UCPs, UCP2, 4 and 5 are significantly reduced in AD brain tissue and a specific UCP4 variant has been associated to an increased risk of developing AD. Few studies modulating the expression of UCP4 in astrocytes or neurons have highlighted protective effects against neurodegeneration and aging, suggesting that pharmacological strategies aimed at activating UCPs, such as protonophoric uncouplers, hold promise for therapeutic interventions in AD and other neurodegenerative diseases. Despite significant advances, our understanding of UCPs in brain metabolism remains in its early stages, emphasizing the need for further research to unravel their biological functions in the brain and their therapeutic potential. Show less
đź“„ PDF DOI: 10.3389/fnins.2024.1483708
ROS amino-acid mitochondria review
R.R. Zhou, C. Alarcón, C. Nadal +374 more · 2021 · Cancers · MDPI · added 2026-04-20
R.R. Zhou, C. Alarcón, C. Nadal, C. Van Poznak, J. Massagué, J.M. Angelastro, P.D. Canoll, J. Kuo, M. Weicker, A. Costa, J.N. Bruce, L. A Greene, R. Piva, E. Pellegrino, M. Mattioli, L. Agnelli, L. Lombardi, F. Boccalatte, G. Costa, B.A. Ruggeri, M. Cheng, R. Chiarle, S.E. Monaco, M. Szabolcs, L.A. Greene, W.J. Oh, V. Rishi, A. Orosz, M.J. Gerdes, C. Vinson, Z. Sheng, L. Li, L.J. Zhu, T.W. Smith, A. Demers, A.H. Ross, R.P. Moser, M.R. Green, M.S. Carro, W.K. Lim, M.J. Alvarez, R.J. Bollo, X. Zhao, E.Y. Snyder, E.P. Sulman, S.L. Anne, F. Doetsch, H. Colman, J. Rousseau, V. Gagné, M. Labuda, C. Beaubois, D. Sinnett, C. Laverdière, A. Moghrabi, S.E. Sallan, L.B. Silverman, D. Neuberg, T.R. Sarkar, S. Sharan, J. Wang, S.A. Pawar, C.A. Cantwell, P.F. Johnson, D.K. Morrison, J.-M. Wang, E. Sterneck, M. Hu, B. Wang, D. Qian, L. Zhang, X. Song, D.X. Liu, Y.-H. Wang, W.-J. Wu, W.-J. Wang, H.-Y. Huang, W.-M. Li, B.-W. Yeh, T.-F. Wu, Y.-L. Shiue, J.J.-C. Sheu, S. Ishihara, M. Yasuda, A. Ishizu, M. Ishikawa, H. Shirato, H. Haga, A. Nukuda, H. Endoh, T. Mizutani, K. Kawabata, S. Banerjee, N. Aykin-Burns, K.J. Krager, S.K. Shah, S.B. Melnyk, M. Hauer-Jensen, J.D. Gardiner, L.M. Abegglen, X. Huang, B.E. Carter, E.A. Schackmann, M. Stucki, C.N. Paxton, R.L. Randall, J.F. Amatruda, A.R. Putnam, Y. Zhang, H.-R. Wang, J.L. Wrana, S. Ben-Shmuel, R. Rashed, R. Rostoker, E. Isakov, Z. Shen-Orr, D. Leroith, C.-F. Li, Y.-Y. Chu, T.-C. Hour, C.-J. Yen, W.-C. Chang, Z.J. Messenger, J.R. Hall, D.D. Jima, J.S. House, H.W. Tam, D.A. Tokarz, R.C. Smart, D. Liu, X.-X. Zhang, M.-C. Li, C.-H. Cao, D.-Y. Wan, B.-X. Xi, J.-H. Tan, Z.-Y. Yang, X.-X. Feng, J. Feldheim, A.F. Kessler, D. Schmitt, L. Wilczek, T. Linsenmann, M. Dahlmann, C.M. Monoranu, R.-I. Ernestus, C. Hagemann, M. Löhr, F. Wang, Y. Gao, L. Tang, K. Ning, N. Geng, H. Zhang, Y. Li, F. Liu, F. Li, Q. Du, Z. Tan, F. Shi, M. Tang, L. Xie, L. Zhao, J. Hu, M. Zhou, A. Bode, D. Wang, X. Cheng, M. Guo, W. Zhao, J. Qiu, Y. Zheng, M. Meng, X. Ping, X. Chen, X. Ruan, X. Liu, Y. Xue, L. Shao, C. Yang, L. Zhu, Y. Yang, Z. Li, B. Yu, H. Wu, J. Gu, D. Zhou, W. Cheng, Y. Wang, Q. Wang, X. Wang, T. Kudo, M.T. Prentzell, S.R. Mohapatra, F. Sahm, Z. Zhao, I. Grummt, W. Wick, C.A. Opitz, M. Platten, E.W. Green, Z.-Y. Hua, J.N. Hansen, M. He, S.-K. Dai, Y. Choi, M.D. Fulton, S.M. Lloyd, M. Szemes, J. Sen, H.-F. Ding, A. Arias, M.W. Lamé, L. Santarelli, R. Hen, C.C. Cates, A.D. Arias, L.S.N. Wong, M. Sidorov, G. Cayanan, D.J. Rowland, J. Fung, G. Karpel-Massler, M.D. Siegelin, B.A. Horst, C. Shu, L. Chau, T. Tsujiuchi, P. Canoll, X. Sun, P. Jefferson, Q. Zhou, M. Olive, S.C. Williams, C. Dezan, A.W. Reinke, J. Baek, O. Ashenberg, A.E. Keating, C.R. Vinson, T. Hai, S.M. Boyd, E. Dupont, A. Prochiantz, A. Joliot, A.M. Sonabend, J. Yun, L. Lei, R. Leung, C. Soderquist, C. Crisman, B.J. Gill, A. Carminucci, J. Sisti, M. Castelli, J.-F. Beaulieu, D. Ménard, W. Chai, I. Ullah, K. Chung, S. Bae, C. Kim, B. Choi, H.Y. Nam, S.H. Kim, C.-O. Yun, K.Y. Lee, S. Rodrigues-Ferreira, H. Moindjie, M.M. Haykal, C. Nahmias, R. Xu, Z. Ji, C. Xu, J. Zhu, N.J. Caron, S.P. Quenneville, J.P. Tremblay, S.Y. Van Der Zanden, X. Qiao, J. Neefjes, F. A Fornari, W.D. Jarvis, S. Grant, M.S. Orr, J.K. Randolph, F.K. White, V.R. Mumaw, E.T. Lovings, R.H. Freeman, D. A Gewirtz, A. Bojko, J. Czarnecka-Herok, A. Charzynska, M. Dabrowski, E. Sikora, T. Kuilman, C. Michaloglou, L.C. Vredeveld, S. Douma, R. Van Doorn, C.J. Desmet, L.A. Aarden, W.J. Mooi, D.S. Peeper, E.S. Hungness, G.-J. Luo, T.A. Pritts, B.W. Robb, D. Hershko, P.-O. Hasselgren, M.Y. Taher, D.M. Davies, J. Maher, J. David, C. Dominguez, D.H. Hamilton, C. Palena, J. Al Sarraj, G. Thiel, F. Siu, C. Chen, C. Zhong, M.S. Kilberg, M. Chiu, G. Taurino, M.G. Bianchi, O. Bussolati, S.P. Wheatley, D.C. Altieri, N.M. Warrier, P. Agarwal, P. Kumar, D.M. García, N. Manero-Rupérez, R. Quesada, L. Korrodi-Gregório, V. Soto-Cerrato, D. Merino, D. Dluzen, G. Li, D. Tacelosky, M. Moreau, W. Li, C. Fiorese, A.M. Schulz, Y.-F. Lin, N. Rosin, M.W. Pellegrino, C.M. Haynes, B. Madarampalli, Y. Yuan, K. Lengel, Y. Xu, J. Yang, Z. Lu, I.K. Mann, R. Chatterjee, J. Zhao, X. He, M.T. Weirauch, T.R. Hughes, M.A. Summers, M.M. McDonald, P.I. Croucher, S.-Y. Park, J.-S. Nam, K.J. Kurppa, Y. Liu, C. To, T. Zhang, M. Fan, A. Vajdi, E.H. Knelson, Y. Xie, K. Lim, P. Cejas Show less
Simple Summary The gene-regulatory factors ATF5, CEBPB and CEBPD promote survival, growth, metastasis and treatment resistance of a range of cancer cell types. Presently, no drugs target all three at Show more
Simple Summary The gene-regulatory factors ATF5, CEBPB and CEBPD promote survival, growth, metastasis and treatment resistance of a range of cancer cell types. Presently, no drugs target all three at once. Here, with the aim of treating cancers, we designed novel cell-penetrating peptides that interact with and inactivate all three. The peptides Bpep and Dpep kill a range of cancer cell types in culture and in animals. In animals with tumors, they also significantly increase survival time. In contrast, they do not affect survival of non-cancer cells and have no apparent side effects in animals. The peptides work in combination with other anti-cancer treatments. Mechanism studies of how the peptides kill cancer cells indicate a decrease in survival proteins and increase in death proteins. These studies support the potential of Bpep and Dpep as novel, safe agents for the treatment of a variety of cancer types, both as mono- and combination therapies. Abstract Transcription factors are key players underlying cancer formation, growth, survival, metastasis and treatment resistance, yet few drugs exist to directly target them. Here, we characterized the in vitro and in vivo anti-cancer efficacy of novel synthetic cell-penetrating peptides (Bpep and Dpep) designed to interfere with the formation of active leucine-zipper-based dimers by CEBPB and CEBPD, transcription factors implicated in multiple malignancies. Both peptides similarly promoted apoptosis of multiple tumor lines of varying origins, without such effects on non-transformed cells. Combined with other treatments (radiation, Taxol, chloroquine, doxorubicin), the peptides acted additively to synergistically and were fully active on Taxol-resistant cells. The peptides suppressed expression of known direct CEBPB/CEBPD targets IL6 , IL8 and asparagine synthetase ( ASNS ), supporting their inhibition of transcriptional activation. Mechanisms by which the peptides trigger apoptosis included depletion of pro-survival survivin and a required elevation of pro-apoptotic BMF. Bpep and Dpep significantly slowed tumor growth in mouse models without evident side effects. Dpep significantly prolonged survival in xenograft models. These findings indicate the efficacy and potential of Bpep and Dpep as novel agents to treat a variety of cancers as mono- or combination therapies. Show less
đź“„ PDF DOI: 10.3390/cancers13102504
JP Ježek, AGW Leslie, R Lutter +1993 more · 2018 · Antioxidants & redox signaling · added 2026-04-20
JP Ježek, AGW Leslie, R Lutter, JE Walker, AE Adams, AM Carroll, PG Fallon, RK Porter, O Hanrahan, DN Nolan, HP Voorheis, P Fallon, OM Kelly, C Affourtit, MD Brand, M Jastroch, C Aguer, BD Piccolo, O Fiehn, SH Adams, ME Harper, L Alán, K Smolková, E Kronusová, J Šantorová, P Ježek, EM Allister, CA Robson-Doucette, KJ Prentice, AB Hardy, S Sultan, HY Gaisano, D Kong, P Gilon, PL Herrera, BB Lowell, MB Wheeler, R Amat, G Solanes, M Giralt, F Villarroya, ZB Andrews, ZW Liu, N Walllingford, DM Erion, E Borok, JM Friedman, MH Tschöp, M Shanabrough, G Cline, GI Shulman, A Coppola, XB Gao, TL Horvath, S Diano, MA Aon, S Cortassa, E Marbán, B O'Rourke, H Aquila, TA Link, M Klingenberg, D Arsenijevic, H Onuma, C Pecqueur, S Raimbault, BS Manning, B Miroux, E Couplan, MC Alves-Guerra, M Goubern, R Surwit, F Bouillaud, D Richard, S Collins, D Ricquier, V Ayyasamy, KM Owens, MM Desouki, P Liang, A Bakin, K Thangaraj, DJ Buchsbaum, AF LoBuglio, KK Singh, V Azzu, EP Breen, N Parker, G Baffy, Z Derdak, SC Robson, Y Bai, X Bai, AV Medvedev, M Misukonis, JB Weinberg, W Cao, J Robidoux, LM Floering, KW Daniel, KA Ball, AW Nelson, DG Foster, RO Poyton, J Barlow, V Hirschberg Jensen, CJ Barnstable, R Reddy, H Li, W Basu Ball, S Kar, M Mukherjee, AG Chande, R Mukhopadhyaya, PK Das, JM Baughman, F Perocchi, HS Girgis, M Plovanich, CA Belcher-Timme, Y Sancak, XR Bao, L Strittmatter, O Goldberger, RL Bogorad, V Koteliansky, VK Mootha, V Beck, M Jabůrek, EE Pohl, T Demina, A Rupprecht, EL Bell, TA Klimova, J Eisenbart, CT Moraes, MP Murphy, GRS Budinger, NS Chandel, MJ Berardi, JJ Chou, WM Shih, SC Harrison, M Bertolotti, G Farinelli, M Galli, A Aiuti, R Sitia, J Blanc, B Esposito, S Rousset, P Gourdy, A Tedgui, Z Mallat, L Bleier, S Dröse, M Board, C Lopez, C van den Bos, R Callaghan, K Clarke, C Carr, AI Bondarenko, W Parichatikanond, CT Madreiter, R Rost, M Waldeck-Weiermair, R Malli, WF Graier, J Borecký, D Siemen, O Boss, S Samec, A Paoloni-Giacobino, C Rossier, A Dulloo, J Seydoux, P Muzzin, JP Giacobino, S Boudina, S Sena, BT O'Neill, P Tathireddy, ME Young, ED Abel, H Theobald, X Sheng, JJ Wright, XH Xia, S Aziz, JI Johnson, H Bugger, VG Zaha, TC Esteves, J Brandi, D Cecconi, M Cordani, M Torrens-Mas, R Pacchiana, E Dalla Pozza, G Butera, M Manfredi, E Marengo, J Oliver, P Roca, I Dando, M Donadelli, MO Breckwoldt, FMJ Pfister, PM Bradley, P Marinković, PR Williams, MS Brill, B Plomer, A Schmalz, DK St Clair, R Naumann, O Griesbeck, M Schwarzländer, L Godinho, FM Bareyre, TP Dick, M Kerschensteiner, T Misgeld, W Pilgrim, KJ Clarke, C Yssel, M Farrell, J Zhou, PV Murphy, PS Brookes, JA Buckingham, A Vidal-Puig, AP Halestrap, TE Gunter, DG Nicholls, P Bernardi, JJ Lemasters, A Bugge, M Siersbæk, MS Madsen, A Göndör, C Rougier, S Mandrup, C Guzman, C Zechner, M Palmeri, KS Russell, RR Russell, JA Cabrera, EA Ziemba, R Colbert, RF Kelly, M Kuskowski, EA Arriaga, W Sluiter, DJ Duncker, HB Ward, EO McFalls, V Calegari, CC Zoppi, L Rezende, L Silveira, E Carneiro, AC Boschero, B Cannon, IG Shabalina, TV Kramarova, N Petrovic, J Nedergaard, A Caron, SM Labbé, S Carter, MC Roy, R Lecomte, F Picard, LR Haines, TW Pearson, CM Walsh, CM Brennan, E Casanova, L Baselga-Escudero, A Ribas-Latre, A Arola-Arnal, C Bladé, L Arola, MJ Salvadó, HZ Chae, H Oubrahim, JW Park, SG Rhee, PB Chock, CB Chan, SL Chan, D Liu, GA Kyriazis, P Bagsiyao, X Ouyang, MP Mattson, L Chaudhuri, RK Srivastava, F Kos, PA Shrikant, M Che, R Wang, X Li, HY Wang, XFS Zheng, C Chen, K Wang, J Chen, J Guo, Y Yin, X Cai, X Guo, G Wang, R Yang, L Zhu, Y Zhang, J Wang, Y Xiang, C Weng, K Zen, J Zhang, CY Zhang, Y Chen, J Liu, Y Zheng, Z Wang, S Gu, J Tan, Q Jing, H Yang, J Cheng, G Nanayakkara, Y Shao, R Cueto, L Wang, WY Yang, Y Tian, H Wang, X Yang, N Cheurfa, D Dubois-Laforgue, DAF Ferrarezi, AF Reis, GM Brenner, C Bouche, C Le Feuvre, F Fumeron, J Timsit, M Marre, G Velho, SY Cho, D Seo, WG Kim, S Lee, YS Cho, JH Lee, KH Jung, SH Moon, YS Choe, KH Lee, ET Chouchani, L Kazak, MP Jedrychowski, GZ Lu, BK Erickson, J Szpyt, KA Pierce, D Laznik-Bogoslavski, R Vetrivelan, CB Clish, AJ Robinson, SP Gygi, BM Spiegelman, C Methner, G Buonincontri, CH Hu, A Logan, SJ Sawiak, T Krieg, VR Pell, E Gaude, D Aksentijević, SY Sundier, EL Robb, SM Nadtochiy, ENJ Ord, AC Smith, F Eyassu, R Shirley, C-H Hu, AJ Dare, AM James, S Rogatti, RC Hartley, S Eaton, ASH Costa, SM Davidson, MR Duchen, K Saeb-Parsy, MJ Shattock, LM Work, C Frezza, YC Chuang, TK Lin, HY Huang, WN Chang, CW Liou, SD Chen, AY Chang, SH Chan, L Contreras, E Rial, S Cerdan, J Satrustegui, E Paradis, A Corcoran, TG Cotter, D Cosentino-Gomes, N Rocco-Machado, JR Meyer-Fernandes, LF Costa Rosa, R Curi, C Murphy, P Newsholme, MDM Gonzalez-Barroso, PG Crichton, Y Lee, ERS Kunji, MD Cruz, S Ledbetter, S Chowdhury, AK Tiwari, N Momi, RK Wali, C Bliss, C Huang, D Lichtenstein, S Bhattacharya, A Varma-Wilson, V Backman, HK Roy, M D'Adamo, L Perego, M Cardellini, MA Marini, S Frontoni, F Andreozzi, A Sciacqua, 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Hou, Y Ding, T Zhang, C Shi, W Fu, Z Cai, F Yin, H Sancheti, E Cadenas, H Yoshitomi, K Yamazaki, I Tanaka, T Liu, SB Jin, C Ning, U Lendahl, M Nistér, SX Yu, CT Du, W Chen, QQ Lei, N Li, S Qi, XJ Zhang, GQ Hu, XM Deng, WY Han, YJ Yang, XX Yu, W Mao, A Zhong, P Schow, J Brush, SW Sherwood, G Pan, P Perret, O Peroni, YB Kim, XX Zheng, R Shen, CT Lin, JA Porco, HJ Zhang, W Zhao, S Venkataraman, MEC Robbins, GR Buettner, KC Kregel, LW Oberley, I Khvorostov, JS Hong, Y Oktay, L Vergnes, E Nuebel, PN Wahjudi, K Setoguchi, A Do, HJ Jung, JM McCaffery, IJ Kurland, K Reue, WNP Lee, CM Koehler, MA Teitell, K Zhang, Z Song, G Zheng, J Lyu, S Liu, J Huang, C Liu, D Xiang, M Xie, Q Zeng, M Zhou, PKH Tam, KSL Lam, B Huang, Y Liang, D Wu, Y Zhou, T Cai, J Xu, L Jiang, J Wu, Q Sun, R Zhu, A Ebner, T Haselgrübler, HJ Gruber, P Hinterdorfer Show less
Abstract Significance: Mitochondria are the energetic, metabolic, redox, and information signaling centers of the cell. Substrate pressure, mitochondrial network dynamics, and cristae morphology Show more
Abstract Significance: Mitochondria are the energetic, metabolic, redox, and information signaling centers of the cell. Substrate pressure, mitochondrial network dynamics, and cristae morphology state are integrated by the protonmotive force Δ p or its potential component, Δ Ψ , which are attenuated by proton backflux into the matrix, termed uncoupling. The mitochondrial uncoupling proteins (UCP1–5) play an eminent role in the regulation of each of the mentioned aspects, being involved in numerous physiological events including redox signaling. Recent Advances: UCP2 structure, including purine nucleotide and fatty acid (FA) binding sites, strongly support the FA cycling mechanism: UCP2 expels FA anions, whereas uncoupling is achieved by the membrane backflux of protonated FA. Nascent FAs, cleaved by phospholipases, are preferential. The resulting Δ p dissipation decreases superoxide formation dependent on Δ p . UCP-mediated antioxidant protection and its impairment are expected to play a major role in cell physiology and pathology. Moreover, UCP2-mediated aspartate, oxaloacetate, and malate antiport with phosphate is expected to alter metabolism of cancer cells. Critical Issues: A wide range of UCP antioxidant effects and participations in redox signaling have been reported; however, mechanisms of UCP activation are still debated. Switching off/on the UCP2 protonophoretic function might serve as redox signaling either by employing/releasing the extra capacity of cell antioxidant systems or by directly increasing/decreasing mitochondrial superoxide sources. Rapid UCP2 degradation, FA levels, elevation of purine nucleotides, decreased Mg 2+ , or increased pyruvate accumulation may initiate UCP-mediated redox signaling. Future Directions: Issues such as UCP2 participation in glucose sensing, neuronal (synaptic) function, and immune cell activation should be elucidated. Antioxid. Redox Signal. 29, 667–714. Show less
đź“„ PDF DOI: 10.1089/ars.2017.7225
mitochondria