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Title:
Molecular mechanisms of cell death: central implication of ATP synthase in mitochondrial permeability transition | Oncogene
Description:
The term mitochondrial permeability transition (MPT) is commonly used to indicate an abrupt increase in the permeability of the inner mitochondrial membrane to low molecular weight solutes. Widespread MPT has catastrophic consequences for the cell, de facto marking the boundary between cellular life and death. MPT results indeed in the structural and functional collapse of mitochondria, an event that commits cells to suicide via regulated necrosis or apoptosis. MPT has a central role in the etiology of both acute and chronic diseases characterized by the loss of post-mitotic cells. Moreover, cancer cells are often relatively insensitive to the induction of MPT, underlying their increased resistance to potentially lethal cues. Thus, intense efforts have been dedicated not only at the understanding of MPT in mechanistic terms, but also at the development of pharmacological MPT modulators. In this setting, multiple mitochondrial and extramitochondrial proteins have been suspected to critically regulate the MPT. So far, however, only peptidylprolyl isomerase F (best known as cyclophilin D) appears to constitute a key component of the so-called permeability transition pore complex (PTPC), the supramolecular entity that is believed to mediate MPT. Here, after reviewing the structural and functional features of the PTPC, we summarize recent findings suggesting that another of its core components is represented by the c subunit of mitochondrial ATP synthase.
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Keywords {🔍}
google, scholar, cas, mitochondrial, cell, permeability, transition, pore, death, synthase, atp, biol, apoptosis, mitochondria, nature, galluzzi, cancer, kroemer, biochem, oncogene, sci, chem, mol, proc, natl, acad, usa, biophys, nat, cyclophilin, nucleotide, protein, article, rev, adenine, membrane, role, subunit, bax, res, febs, molecular, induction, complex, inhibition, biochim, acta, chinopoulos, kepp, cells,
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nature portfolio permissions reprints privacy policy gsk-3beta-mediated myocardial protection advertising atp/adp-mediated matrix ca siric cancer research social media autophagy-inflammation-cell death axis cancer research institutes glycogen synthase kinase-3beta voltage-dependent anion channel voltage-dependent anion channels european research council mg2+-induced adp-dependent inhibition development protect pancreatic beta-cells italy active/inactive state transitions slow active/inactive transition induced large-amplitude swelling reverses bcl-2-mediated cytoprotection ca2+-dependent cell survival reversible antiport-uniport conversion cancer research bid-induced conformational change mitochondrial f1f0-atp synthase matrix substrate-level phosphorylation mitochondrial f1f0-atp synthases nature 2009 nature 2011 nature 2005 nature 2004 nature 1999 nature 1961 nature 1997 nature 2013 nature 1981 nature 2006 nature peripheral-type benzodiazepine receptor ameliorate cardio-apoptotic risks mitochondrial-dependent cell death cgmp-dependent protein kinase anti-apoptotic mcl-1 localizes cytokine-induced cell death phosphate-induced mitochondrial swelling acetaminophen-induced oxidant stress potentiates chemotherapy-induced cytotoxicity anti-apoptotic bcl-2 proteins
Questions {❓}
- Is supercomplex organization of the respiratory chain required for optimal electron transfer activity?
- Modulation of the mitochondrial permeability transition by cyclophilin D: moving closer to F(0)-F(1) ATP synthase?
- The apoptotic pore on mitochondria: are we breaking through or still stuck?
- What is the mitochondrial permeability transition pore?
- What makes you can also break you, part II: mitochondrial permeability transition pore formation by dimers of the F1FO ATP-synthase?
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External Links {🔗}(248)
- How much does https://doi.org/10.1038/onc.2014.462 pull in?
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- What's the total monthly financial gain of http://scholar.google.com/scholar_lookup?&title=The%20apoptosis-necrosis%20paradox.%20Apoptogenic%20proteases%20activated%20after%20mitochondrial%20permeability%20transition%20determine%20the%20mode%20of%20cell%20death&journal=Oncogene&volume=15&pages=1573-1581&publication_year=1997&author=Hirsch%2CT&author=Marchetti%2CP&author=Susin%2CSA&author=Dallaporta%2CB&author=Zamzami%2CN&author=Marzo%2CI?
- What's the financial gain of http://scholar.google.com/scholar_lookup?&title=Cyclophilin%20D%20is%20a%20component%20of%20mitochondrial%20permeability%20transition%20and%20mediates%20neuronal%20cell%20death%20after%20focal%20cerebral%20ischemia&journal=Proc%20Natl%20Acad%20Sci%20USA&volume=102&pages=12005-12010&publication_year=2005&author=Schinzel%2CAC&author=Takeuchi%2CO&author=Huang%2CZ&author=Fisher%2CJK&author=Zhou%2CZ&author=Rubens%2CJ?
- Revenue of http://scholar.google.com/scholar_lookup?&title=Loss%20of%20cyclophilin%20D%20reveals%20a%20critical%20role%20for%20mitochondrial%20permeability%20transition%20in%20cell%20death&journal=Nature&volume=434&pages=658-662&publication_year=2005&author=Baines%2CCP&author=Kaiser%2CRA&author=Purcell%2CNH&author=Blair%2CNS&author=Osinska%2CH&author=Hambleton%2CMA
- Learn about the earnings of http://scholar.google.com/scholar_lookup?&title=Cyclophilin%20D-dependent%20mitochondrial%20permeability%20transition%20regulates%20some%20necrotic%20but%20not%20apoptotic%20cell%20death&journal=Nature&volume=434&pages=652-658&publication_year=2005&author=Nakagawa%2CT&author=Shimizu%2CS&author=Watanabe%2CT&author=Yamaguchi%2CO&author=Otsu%2CK&author=Yamagata%2CH
- How much cash flow does http://scholar.google.com/scholar_lookup?&title=Bax%20regulates%20primary%20necrosis%20through%20mitochondrial%20dynamics&journal=Proc%20Natl%20Acad%20Sci%20USA&volume=109&pages=6566-6571&publication_year=2012&author=Whelan%2CRS&author=Konstantinidis%2CK&author=Wei%2CAC&author=Chen%2CY&author=Reyna%2CDE&author=Jha%2CS have monthly?
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- What's http://scholar.google.com/scholar_lookup?&title=Cyclophilin%20D%20deficiency%20protects%20against%20acetaminophen-induced%20oxidant%20stress%20and%20liver%20injury&journal=Free%20Radic%20Res&volume=45&pages=156-164&publication_year=2011&author=Ramachandran%2CA&author=Lebofsky%2CM&author=Baines%2CCP&author=Lemasters%2CJJ&author=Jaeschke%2CH's gross income?
- What's the income generated by http://scholar.google.com/scholar_lookup?&title=Pharmacologic%20targeting%20or%20genetic%20deletion%20of%20mitochondrial%20cyclophilin%20D%20protects%20from%20NSAID-induced%20small%20intestinal%20ulceration%20in%20mice&journal=Toxicol%20Sci&volume=118&pages=276-285&publication_year=2010&author=LoGuidice%2CA&author=Ramirez-Alcantara%2CV&author=Proli%2CA&author=Gavillet%2CB&author=Boelsterli%2CUA each month?
- How much revenue does http://scholar.google.com/scholar_lookup?&title=Mitochondrial%20permeability%20transition%20as%20a%20novel%20principle%20of%20hepatorenal%20toxicity%20in%20vivo&journal=Apoptosis&volume=7&pages=395-405&publication_year=2002&author=Haouzi%2CD&author=Cohen%2CI&author=Vieira%2CHL&author=Poncet%2CD&author=Boya%2CP&author=Castedo%2CM produce monthly?
- http://scholar.google.com/scholar_lookup?&title=Targeting%20cyclophilin%20D%20and%20the%20mitochondrial%20permeability%20transition%20enhances%20beta-cell%20survival%20and%20prevents%20diabetes%20in%20Pdx1%20deficiency&journal=Proc%20Natl%20Acad%20Sci%20USA&volume=107&pages=10214-10219&publication_year=2010&author=Fujimoto%2CK&author=Chen%2CY&author=Polonsky%2CKS&author=Dorn%2CGW's financial summary
- How much revenue does http://scholar.google.com/scholar_lookup?&title=Genetic%20ablation%20of%20cyclophilin%20D%20rescues%20mitochondrial%20defects%20and%20prevents%20muscle%20apoptosis%20in%20collagen%20VI%20myopathic%20mice&journal=Hum%20Mol%20Genet&volume=18&pages=2024-2031&publication_year=2009&author=Palma%2CE&author=Tiepolo%2CT&author=Angelin%2CA&author=Sabatelli%2CP&author=Maraldi%2CNM&author=Basso%2CE generate?
- http://scholar.google.com/scholar_lookup?&title=Genetic%20and%20pharmacologic%20inhibition%20of%20mitochondrial-dependent%20necrosis%20attenuates%20muscular%20dystrophy&journal=Nat%20Med&volume=14&pages=442-447&publication_year=2008&author=Millay%2CDP&author=Sargent%2CMA&author=Osinska%2CH&author=Baines%2CCP&author=Barton%2CER&author=Vuagniaux%2CG's financial summary
- http://scholar.google.com/scholar_lookup?&title=Molecular%20mechanisms%20of%20cisplatin%20resistance&journal=Oncogene&volume=31&pages=1869-1883&publication_year=2012&author=Galluzzi%2CL&author=Senovilla%2CL&author=Vitale%2CI&author=Michels%2CJ&author=Martins%2CI&author=Kepp%2CO's financial summary
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- What's the financial intake of http://scholar.google.com/scholar_lookup?&title=Targeting%20Bax%20interaction%20sites%20reveals%20that%20only%20homo-oligomerization%20sites%20are%20essential%20for%20its%20activation&journal=Cell%20Death%20Differ&volume=20&pages=744-754&publication_year=2013&author=Peng%2CR&author=Tong%2CJS&author=Li%2CH&author=Yue%2CB&author=Zou%2CF&author=Yu%2CJ?
- How much revenue does http://scholar.google.com/scholar_lookup?&title=Mitochondrial%20membrane%20permeabilization%20in%20neuronal%20injury&journal=Nat%20Rev%20Neurosci&volume=10&pages=481-494&publication_year=2009&author=Galluzzi%2CL&author=Blomgren%2CK&author=Kroemer%2CG bring in?
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- What's the financial gain of http://scholar.google.com/scholar_lookup?&title=Inhibition%20of%20the%20mitochondrial%20permeability%20transition%20for%20cytoprotection%3A%20direct%20versus%20indirect%20Mechanisms&journal=Biochem%20Res%20Int&volume=2012&publication_year=2012&author=Martel%2CC&author=Huynh%20le%2CH&author=Garnier%2CA&author=Ventura-Clapier%2CR&author=Brenner%2CC?
- How much does http://scholar.google.com/scholar_lookup?&title=Cell%20death%20assays%20for%20drug%20discovery&journal=Nat%20Rev%20Drug%20Discov&volume=10&pages=221-237&publication_year=2011&author=Kepp%2CO&author=Galluzzi%2CL&author=Lipinski%2CM&author=Yuan%2CJ&author=Kroemer%2CG gross monthly?
- What's the income generated by http://scholar.google.com/scholar_lookup?&title=Individuality%3A%20the%20barrier%20to%20optimal%20immunosuppression&journal=Nat%20Rev%20Immunol&volume=3&pages=831-838&publication_year=2003&author=Kahan%2CBD each month?
- Income figures for http://scholar.google.com/scholar_lookup?&title=The%20apoptotic%20pore%20on%20mitochondria%3A%20are%20we%20breaking%20through%20or%20still%20stuck%3F&journal=Cell%20Death%20Differ&volume=21&pages=187-191&publication_year=2014&author=Borner%2CC&author=Andrews%2CDW
- http://scholar.google.com/scholar_lookup?&title=The%20mitochondrial%20megachannel%20is%20the%20permeability%20transition%20pore&journal=J%20Bioenerg%20Biomembr&volume=24&pages=111-117&publication_year=1992&author=Szabo%2CI&author=Zoratti%2CM's total income per month
- How much revenue does http://scholar.google.com/scholar_lookup?&title=Modulation%20of%20the%20mitochondrial%20megachannel%20by%20divalent%20cations%20and%20protons&journal=J%20Biol%20Chem&volume=267&pages=2940-2946&publication_year=1992&author=Szabo%2CI&author=Bernardi%2CP&author=Zoratti%2CM generate?
- Monthly income for http://scholar.google.com/scholar_lookup?&title=The%20mitochondrial%20permeability%20transition%20pore%20may%20comprise%20VDAC%20molecules.%20I.%20Binary%20structure%20and%20voltage%20dependence%20of%20the%20pore&journal=FEBS%20Lett&volume=330&pages=201-205&publication_year=1993&author=Szabo%2CI&author=Zoratti%2CM
- http://scholar.google.com/scholar_lookup?&title=The%20mitochondrial%20permeability%20transition%20pore%20may%20comprise%20VDAC%20molecules.%20II.%20The%20electrophysiological%20properties%20of%20VDAC%20are%20compatible%20with%20those%20of%20the%20mitochondrial%20megachannel&journal=FEBS%20Lett&volume=330&pages=206-210&publication_year=1993&author=Szabo%2CI&author=De%20Pinto%2CV&author=Zoratti%2CM's financial summary
- How much does http://scholar.google.com/scholar_lookup?&title=Isolation%20of%20the%20mitochondrial%20benzodiazepine%20receptor%3A%20association%20with%20the%20voltage-dependent%20anion%20channel%20and%20the%20adenine%20nucleotide%20carrier&journal=Proc%20Natl%20Acad%20Sci%20USA&volume=89&pages=3170-3174&publication_year=1992&author=McEnery%2CMW&author=Snowman%2CAM&author=Trifiletti%2CRR&author=Snyder%2CSH gross monthly?
- Get to know http://scholar.google.com/scholar_lookup?&title=Complexes%20between%20kinases%2C%20mitochondrial%20porin%20and%20adenylate%20translocator%20in%20rat%20brain%20resemble%20the%20permeability%20transition%20pore&journal=FEBS%20Lett&volume=396&pages=189-195&publication_year=1996&author=Beutner%2CG&author=Ruck%2CA&author=Riede%2CB&author=Welte%2CW&author=Brdiczka%2CD's earnings
- What's the financial outcome of http://scholar.google.com/scholar_lookup?&title=Complexes%20between%20porin%2C%20hexokinase%2C%20mitochondrial%20creatine%20kinase%20and%20adenylate%20translocator%20display%20properties%20of%20the%20permeability%20transition%20pore.%20Implication%20for%20regulation%20of%20permeability%20transition%20by%20the%20kinases&journal=Biochim%20Biophys%20Acta&volume=1368&pages=7-18&publication_year=1998&author=Beutner%2CG&author=Ruck%2CA&author=Riede%2CB&author=Brdiczka%2CD?
- See how much http://scholar.google.com/scholar_lookup?&title=Cyclophilin-D%20binds%20strongly%20to%20complexes%20of%20the%20voltage-dependent%20anion%20channel%20and%20the%20adenine%20nucleotide%20translocase%20to%20form%20the%20permeability%20transition%20pore&journal=Eur%20J%20Biochem&volume=258&pages=729-735&publication_year=1998&author=Crompton%2CM&author=Virji%2CS&author=Ward%2CJM makes per month
- Financial intake of http://scholar.google.com/scholar_lookup?&title=Involvement%20of%20cyclophilin%20D%20in%20the%20activation%20of%20a%20mitochondrial%20pore%20by%20Ca2%2B%20and%20oxidant%20stress&journal=Eur%20J%20Biochem&volume=238&pages=166-172&publication_year=1996&author=Tanveer%2CA&author=Virji%2CS&author=Andreeva%2CL&author=Totty%2CNF&author=Hsuan%2CJJ&author=Ward%2CJM
- How much cash flow does http://scholar.google.com/scholar_lookup?&title=Inhibition%20of%20Ca2%28%2B%29-induced%20large-amplitude%20swelling%20of%20liver%20and%20heart%20mitochondria%20by%20cyclosporin%20is%20probably%20caused%20by%20the%20inhibitor%20binding%20to%20mitochondrial-matrix%20peptidyl-prolyl%20cis-trans%20isomerase%20and%20preventing%20it%20interacting%20with%20the%20adenine%20nucleotide%20translocase&journal=Biochem%20J&volume=268&pages=153-160&publication_year=1990&author=Halestrap%2CAP&author=Davidson%2CAM have monthly?
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- How much revenue does http://scholar.google.com/scholar_lookup?&title=The%20ADP%2FATP%20translocator%20is%20not%20essential%20for%20the%20mitochondrial%20permeability%20transition%20pore&journal=Nature&volume=427&pages=461-465&publication_year=2004&author=Kokoszka%2CJE&author=Waymire%2CKG&author=Levy%2CSE&author=Sligh%2CJE&author=Cai%2CJ&author=Jones%2CDP generate?
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