👤 F Bianchi

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Also published as: G. Bianchi, M.G. Bianchi
articles
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, D Lauro, P Sbraccia, M Federici, M Paganelli, AE Pontiroli, R Lauro, F Perticone, F Folli, G Sesti, A Daiber, F Di Lisa, M Oelze, S Kröller-Schön, S Steven, E Schulz, T Münzel, LT Dalgaard, G Andersen, LH Larsen, TIA Sørensen, T Andersen, T Drivsholm, K Borch-Johnsen, J Fleckner, T Hansen, N Din, O Pedersen, C Fiorini, ED Pozza, C Padroni, C Costanzo, M Palmieri, S Dato, F De Rango, P Crocco, G Passarino, G Rose, PBM De Andrade, M Casimir, P Maechler, P De Lange, A Feola, M Ragni, R Senese, M Moreno, A Lombardi, E Silvestri, F Goglia, A Lanni, U De Marchi, C Castelbou, N Demaurex, R De Simone, MA Ajmone-Cat, M Pandolfi, A Bernardo, C De Nuccio, L Minghetti, S Visentin, D De Stefani, A Raffaello, E Teardo, I Szabò, R Rizzuto, T Pozzan, G Den Besten, A Bleeker, A Gerding, K Van Eunen, R Havinga, TH Van Dijk, MH Oosterveer, JW Jonker, AK Groen, DJ Reijngoud, BM Bakker, Z Derdák, P Fülöp, E Sabo, R Tavares, EP Berthiaume, MB Resnick, G Paragh, JR Wands, NM Mark, G Beldi, SS Dhamrait, JW Stephens, JA Cooper, J Acharya, AR Mani, K Moore, GJ Miller, SE Humphries, SJ Hurel, HE Montgomery, JK Jeong, MO Dietrich, HB Ruan, E Kim, S Suyama, K Kelly, E Gyengesi, JL Arbiser, DD Belsham, DA Sarruf, MW Schwartz, AM Bennett, CV Mobbs, WX Ding, M Li, JM Biazik, DG Morgan, F Guo, HM Ni, M Goheen, EL Eskelinen, XM Yin, AS Divakaruni, A Dlasková, L Hlavatá, J Ježek, T Špacek, E Škobisová, U Brandt, RH Du, FF Wu, M Lu, X dong Shu, JH Ding, G Wu, G Hu, CM Duffy, H Xu, JP Nixon, DA Bernlohr, TA Butterick, D Duteil, C Chambon, F Ali, R Malivindi, J Zoll, S Kato, B Geny, P Chambon, D Metzger, C Duval, A Nègre-Salvayre, A Doglio, R Salvayre, L Pénicaud, L Casteilla, F Echeverría, M Ortiz, R Valenzuela, LA Videla, KS Echtay, JL Pakay, MB Jekabsons, AJ Lambert, M Portero-Otín, R Pamplona, AJ Vidal-Puig, S Wang, SJ Roebuck, V Eisner, RR Cupo, E Gao, G Csordás, WS Slovinsky, M Paillard, L Cheng, J Ibetti, SRW Chen, JK Chuprun, JB Hoek, WJ Koch, G Hajnóczky, A Elorza, B Hyde, HK Mikkola, OS Shirihai, Y Emre, C Hurtaud, T Nübel, F Criscuolo, AM Cassard-Doulcier, H Esterbauer, C Schneitler, H Oberkofler, C Ebenbichler, B Paulweber, F Sandhofer, G Ladurner, E Hell, AD Strosberg, JR Patsch, F Krempler, W Patsch, P Esteves, C Ransy, C Esnous, V Lenoir, AL Bulteau, A Lombès, C Prip-Buus, Y Fan, K Futawaka, R Koyama, Y Fukuda, M Hayashi, M Imamoto, T Miyawaki, M Kasahara, T Tagami, K Moriyama, A Fedorenko, PV Lishko, Y Kirichok, C Fleury, M Neverova, O Champigny, C Levi-Meyrueis, MF Seldin, RS Surwit, CH Warden, S Freigang, F Ampenberger, A Weiss, T-D Kanneganti, Y Iwakura, M Hersberger, M Kopf, R Fukumori, T Takarada, Y Kambe, R Nakazato, K Fujikawa, Y Yoneda, M Kou, E Hinoi, DR Gable, S Galetti, A Sarre, H Perreten, N Produit-Zengaffinen, F Assimacopoulos-Jeannet, S Gargiulo, MP Petretta, A Greco, M Panico, M Larobina, M Gramanzini, GG Schiattarella, G Esposito, M Petretta, A Brunetti, A Cuocolo, AO Garlid, JP Jacobs, KD Garlid, ADT Costa, CL Quinlan, SV Pierre, P Dos Santos, M Vařecha, RA Nakashima, DE Orosz, M Modrianský, S Vassanelli, A Georgiadi, MV Boekschoten, M Muller, S Kersten, D Gerö, C Szabo, TM Giardina, JH Steer, SZY Lo, DA Joyce, RE Gimeno, M Dembski, X Weng, N Deng, AW Shyjan, CJ Gimeno, F Iris, SJ Ellis, EA Woolf, LA Tartaglia, C Giorgi, C Agnoletto, C Baldini, A Bononi, M Bonora, S Marchi, S Missiroli, S Patergnani, F Poletti, A Rimessi, B Zavan, P Pinton, B Glancy, LM Hartnell, D Malide, Z-X Yu, CA Combs, PS Connelly, S Subramaniam, RS Balaban, R Gopalakrishna, S Jaken, N Guex, MC Peitsch, F Guillaud, A Kowald, E Klipp, KK Gunter, DR Pfeiffer, J Gutierrez, SW Ballinger, VM Darley-Usmar, A Landar, B Haines, PA Li, RB Hamanaka, SE Weinberg, CR Reczek, P Hanák, M Hara-Chikuma, H Satooka, S Watanabe, T Honda, Y Miyachi, T Watanabe, AS Verkman, R Harmancey, DL Haight, KA Watts, H Taegtmeyer, M Haslip, I Dostanic, Y Huang, MJ Jurczak, P Mannam, F Giordano, SC Erzurum, PJ Lee, DT Hass, AK Hauck, D Hauton, R Evans, G Hermes, D Nagy, M Waterson, A Zsarnovszky, L Varela, M Hajos, AV Hertzel, M Downey, N Kvalheim, AN Higdon, S Barnes, S Hima, S Sreeja, M Hirose, P Schilf, F Lange, J Mayer, G Reichart, P Maity, O Jöhren, M Schwaninger, K Scharffetter-Kochanek, C Sina, CD Sadik, R Köhling, SM Ibrahim, JWM Ho, PWL Ho, WY Zhang, HF Liu, KHH Kwok, DCW Yiu, KH Chan, MHW Kung, DB Ramsden, SL Ho, PW Ho, JW Ho, DH So, ZH Tse, ACY Chu, HM Tse, DHF So, T Hoang, M Kuljanin, MD Smith, M Jelokhani-Niaraki, T Matovic, J Parker, NE Hoffman, HC Chandramoorthy, S Shanmughapriya, XQ Zhang, S Vallem, PJ Doonan, K Malliankaraman, S Guo, S Rajan, JW Elrod, JY Cheung, M Madesh, C Hoffmann, A Zimmermann, A Hinney, AL Volckmar, HW Jarrett, T Fromme, M Klingenspor, Z Huang, J Li, S Du, G Chen, Y Qi, L Huang, L Xiao, P Tong, C Gelly, C Lévi-Meyrueis, Z Chen, LF Iannucci, J Sun, BK Singh, VA Kaddai, PM Yen, RA Sinha, K Imoto, D Kukidome, T Nishikawa, T Matsuhisa, K Sonoda, K Fujisawa, M Yano, H Motoshima, T Taguchi, K Tsuruzoe, T Matsumura, H Ichijo, E Araki, JR Burton, CL Costa, J Zelenka, S Miyamoto, P Di Mascio, MB Zhang, P Burn, K Withers, Y Jeanson, A Carrière, H Engstová, M Bauer, WE Trommer, L Plecitá-Hlavatá, M Žáčková, AE Vercesi, P Arruda, MM Fagian, M Nekvasil, HJ Freisleben, J Hanuš, C Semrad, J Houštěk, Z Drahota, M Modriansky, R Rossignol, T Špaček, E Urbanková, M Růzička, F Ji, T Shen, W Zou, J Jiao, Q Ji, H Ikegami, T Fujisawa, Y Kawabata, M Ono, M Nishino, M Ohishi, T Katsuya, H Rakugi, T Ogihara, D Jiang, L Zhao, DE Clapham, S Jitrapakdee, A Wutthisathapornchai, JC Wallace, MJ MacDonald, DP Jones, H Sies, E Jones, N Gaytan, I Garcia, A Herrera, M Ramos, D Agarwala, M Rana, W Innis-Whitehouse, E Schuenzel, R Gilkerson, S Kajimura, M Saito, F Kamp, JA Hamilton, HV Westerhoff, D Zakim, F Zhang, N Noy, A Kasahara, L Scorrano, D Kim, M Thompson, YM Kim, SJ Kim, R Tatsunami, H Yamamura, T Fukai, M Ushio-Fukai, MS King, M Kerr, R Springett, T Kleine, D Leister, DA Hughes, L Manzke, E Polymeropoulos, T Riemann, M Trzcionka, V Hirschberg, C Klomsiri, PA Karplus, LB Poole, SC Kolwicz, R Tian, L Vong, LE Parton, C Ye, Q Tong, X Hu, B Choi, JC Brüning, H Konishi, E Yamauchi, H Taniguchi, T Yamamoto, H Matsuzaki, Y Takemura, K Ohmae, U Kikkawa, Y Nishizuka, SS Korshunov, OV Korkina, EK Ruuge, VP Skulachev, AA Starkov, A Korwitz, C Merkwirth, R Richter-Dennerlein, SE Tröder, HG Sprenger, PM Quirós, C López-Otín, EI Rugarli, T Langer, A Koziel, W Jarmuszkiewicz, I Sobieraj, AV Kozlov, JR Lancaster, AT Meszaros, A Weidinger, A Kukat, SA Dogan, D Edgar, A Mourier, C Jacoby, P Maiti, J Mauer, C Becker, K Senft, R Wibom, AP Kudin, K Hultenby, U Flögel, S Rosenkranz, WS Kunz, A Trifunovic, R Larbig, S Reda, V Paar, A Trost, J Leitner, S Weichselbaumer, KA Motloch, B Wernly, A Arrer, B Strauss, M Lichtenauer, HA Reitsamer, L Eckardt, G Seebohm, UC Hoppe, LJ Motloch, JE Lee, LM Westrate, H Wu, C Page, GK Voeltz, KU Lee, IK Lee, J Han, DK Song, HS Song, HS Kim, WJ Lee, EH Koh, KH Song, SM Han, MS Kim, IS Park, JY Park, 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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