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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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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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- How much does http://scholar.google.com/scholar_lookup?&title=Viral%20control%20of%20mitochondrial%20apoptosis&journal=PLoS%20Pathog&volume=4&publication_year=2008&author=Galluzzi%2CL&author=Brenner%2CC&author=Morselli%2CE&author=Touat%2CZ&author=Kroemer%2CG bring in each month?
- Income figures for http://scholar.google.com/scholar_lookup?&title=The%20mitochondrial%20phosphate%20carrier%20interacts%20with%20cyclophilin%20D%20and%20may%20play%20a%20key%20role%20in%20the%20permeability%20transition&journal=J%20Biol%20Chem&volume=283&pages=26312-26323&publication_year=2008&author=Leung%2CAW&author=Varanyuwatana%2CP&author=Halestrap%2CAP
- How much does http://scholar.google.com/scholar_lookup?&title=A%20high-throughput%20screening%20for%20mammalian%20cell%20death%20effectors%20identifies%20the%20mitochondrial%20phosphate%20carrier%20as%20a%20regulator%20of%20cytochrome%20c%20release&journal=Oncogene&volume=27&pages=44-54&publication_year=2008&author=Alcala%2CS&author=Klee%2CM&author=Fernandez%2CJ&author=Fleischer%2CA&author=Pimentel-Muinos%2CFX earn?
- What are the earnings of http://scholar.google.com/scholar_lookup?&title=The%20reversible%20antiport-uniport%20conversion%20of%20the%20phosphate%20carrier%20from%20yeast%20mitochondria%20depends%20on%20the%20presence%20of%20a%20single%20cysteine&journal=J%20Biol%20Chem&volume=272&pages=10558-10564&publication_year=1997&author=Schroers%2CA&author=Kramer%2CR&author=Wohlrab%2CH?
- What's the revenue for http://scholar.google.com/scholar_lookup?&title=The%20roles%20of%20phosphate%20and%20the%20phosphate%20carrier%20in%20the%20mitochondrial%20permeability%20transition%20pore&journal=Mitochondrion&volume=12&pages=120-125&publication_year=2012&author=Varanyuwatana%2CP&author=Halestrap%2CAP?
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- What's the financial gain of http://scholar.google.com/scholar_lookup?&title=Dynamic%20evolution%20of%20the%20adenine%20nucleotide%20translocase%20interactome%20during%20chemotherapy-induced%20apoptosis&journal=Oncogene&volume=23&pages=8049-8064&publication_year=2004&author=Verrier%2CF&author=Deniaud%2CA&author=Lebras%2CM&author=Metivier%2CD&author=Kroemer%2CG&author=Mignotte%2CB?
- How much does http://scholar.google.com/scholar_lookup?&title=Mitochondrial%20benzodiazepine%20receptors%20regulate%20steroid%20biosynthesis&journal=Proc%20Natl%20Acad%20Sci%20USA&volume=86&pages=9813-9816&publication_year=1989&author=Mukhin%2CAG&author=Papadopoulos%2CV&author=Costa%2CE&author=Krueger%2CKE generate monthly?
- How much does http://scholar.google.com/scholar_lookup?&title=Protoporphyrin%20IX%2C%20an%20endogenous%20ligand%20of%20the%20peripheral%20benzodiazepine%20receptor%2C%20potentiates%20induction%20of%20the%20mitochondrial%20permeability%20transition%20and%20the%20killing%20of%20cultured%20hepatocytes%20by%20rotenone&journal=J%20Biol%20Chem&volume=269&pages=31041-31046&publication_year=1994&author=Pastorino%2CJG&author=Simbula%2CG&author=Gilfor%2CE&author=Hoek%2CJB&author=Farber%2CJL make?
- How much profit is http://scholar.google.com/scholar_lookup?&title=PK11195%2C%20a%20ligand%20of%20the%20mitochondrial%20benzodiazepine%20receptor%2C%20facilitates%20the%20induction%20of%20apoptosis%20and%20reverses%20Bcl-2-mediated%20cytoprotection&journal=Exp%20Cell%20Res&volume=241&pages=426-434&publication_year=1998&author=Hirsch%2CT&author=Decaudin%2CD&author=Susin%2CSA&author=Marchetti%2CP&author=Larochette%2CN&author=Resche-Rigon%2CM making per month?
- How much does http://scholar.google.com/scholar_lookup?&title=Peripheral-type%20benzodiazepine%20receptor%20ligands%3A%20mitochondrial%20permeability%20transition%20induction%20in%20rat%20cardiac%20tissue&journal=Biochem%20Pharmacol&volume=61&pages=695-705&publication_year=2001&author=Chelli%2CB&author=Falleni%2CA&author=Salvetti%2CF&author=Gremigni%2CV&author=Lucacchini%2CA&author=Martini%2CC pull in monthly?
- How much income is http://scholar.google.com/scholar_lookup?&title=The%20peripheral-type%20benzodiazepine%20receptor%20is%20involved%20in%20control%20of%20Ca2%2B-induced%20permeability%20transition%20pore%20opening%20in%20rat%20brain%20mitochondria&journal=Cell%20Calcium&volume=42&pages=27-39&publication_year=2007&author=Azarashvili%2CT&author=Grachev%2CD&author=Krestinina%2CO&author=Evtodienko%2CY&author=Yurkov%2CI&author=Papadopoulos%2CV earning monthly?
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- How much income does http://scholar.google.com/scholar_lookup?&title=Peripheral%20benzodiazepine%20receptor%20ligands%20reverse%20apoptosis%20resistance%20of%20cancer%20cells%20in%20vitro%20and%20in%20vivo&journal=Cancer%20Res&volume=62&pages=1388-1393&publication_year=2002&author=Decaudin%2CD&author=Castedo%2CM&author=Nemati%2CF&author=Beurdeley-Thomas%2CA&author=De%20Pinieux%2CG&author=Caron%2CA have?
- How much does http://scholar.google.com/scholar_lookup?&title=PK11195%20potently%20sensitizes%20to%20apoptosis%20induction%20independently%20from%20the%20peripheral%20benzodiazepin%20receptor&journal=Oncogene&volume=24&pages=7503-7513&publication_year=2005&author=Gonzalez-Polo%2CRA&author=Carvalho%2CG&author=Braun%2CT&author=Decaudin%2CD&author=Fabre%2CC&author=Larochette%2CN pull in monthly?
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- Income figures for http://scholar.google.com/scholar_lookup?&title=Inhibition%20of%20the%20mitochondrial%20permeability%20transition%20by%20creatine%20kinase%20substrates.%20Requirement%20for%20microcompartmentation&journal=J%20Biol%20Chem&volume=278&pages=17760-17766&publication_year=2003&author=Dolder%2CM&author=Walzel%2CB&author=Speer%2CO&author=Schlattner%2CU&author=Wallimann%2CT
- What's the profit of http://scholar.google.com/scholar_lookup?&title=Isozymes%20of%20mammalian%20hexokinase%3A%20structure%2C%20subcellular%20localization%20and%20metabolic%20function&journal=J%20Exp%20Biol&volume=206&pages=2049-2057&publication_year=2003&author=Wilson%2CJE?
- How much income is http://scholar.google.com/scholar_lookup?&title=Regulation%20of%20hexokinase%20binding%20to%20VDAC&journal=J%20Bioenerg%20Biomembr&volume=40&pages=171-182&publication_year=2008&author=Pastorino%2CJG&author=Hoek%2CJB earning monthly?
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- How much revenue does http://scholar.google.com/scholar_lookup?&title=Disruption%20of%20the%20hexokinase-VDAC%20complex%20for%20tumor%20therapy&journal=Oncogene&volume=27&pages=4633-4635&publication_year=2008&author=Galluzzi%2CL&author=Kepp%2CO&author=Tajeddine%2CN&author=Kroemer%2CG bring in?
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- Earnings of http://scholar.google.com/scholar_lookup?&title=Activation%20of%20glycogen%20synthase%20kinase%203beta%20disrupts%20the%20binding%20of%20hexokinase%20II%20to%20mitochondria%20by%20phosphorylating%20voltage-dependent%20anion%20channel%20and%20potentiates%20chemotherapy-induced%20cytotoxicity&journal=Cancer%20Res&volume=65&pages=10545-10554&publication_year=2005&author=Pastorino%2CJG&author=Hoek%2CJB&author=Shulga%2CN
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- How much income is http://scholar.google.com/scholar_lookup?&title=Anti-apoptotic%20effect%20of%20cGMP%20in%20cultured%20astrocytes%3A%20inhibition%20by%20cGMP-dependent%20protein%20kinase%20of%20mitochondrial%20permeable%20transition%20pore&journal=J%20Biol%20Chem&volume=276&pages=48093-48099&publication_year=2001&author=Takuma%2CK&author=Phuagphong%2CP&author=Lee%2CE&author=Mori%2CK&author=Baba%2CA&author=Matsuda%2CT earning monthly?
- Financial intake of http://scholar.google.com/scholar_lookup?&title=Glycogen%20synthase%20kinase%203%20inhibition%20slows%20mitochondrial%20adenine%20nucleotide%20transport%20and%20regulates%20voltage-dependent%20anion%20channel%20phosphorylation&journal=Circ%20Res&volume=103&pages=983-991&publication_year=2008&author=Das%2CS&author=Wong%2CR&author=Rajapakse%2CN&author=Murphy%2CE&author=Steenbergen%2CC
- How much money does http://scholar.google.com/scholar_lookup?&title=Modulation%20of%20the%20mitochondrial%20permeability%20transition%20pore%20complex%20in%20GSK-3beta-mediated%20myocardial%20protection&journal=J%20Mol%20Cell%20Cardiol&volume=43&pages=564-570&publication_year=2007&author=Nishihara%2CM&author=Miura%2CT&author=Miki%2CT&author=Tanno%2CM&author=Yano%2CT&author=Naitoh%2CK make?
- What's the monthly income of http://scholar.google.com/scholar_lookup?&title=Chemotherapeutic%20induction%20of%20mitochondrial%20oxidative%20stress%20activates%20GSK-3alpha%2Fbeta%20and%20Bax%2C%20leading%20to%20permeability%20transition%20pore%20opening%20and%20tumor%20cell%20death&journal=Cell%20Death%20Dis&volume=3&publication_year=2012&author=Chiara%2CF&author=Gambalunga%2CA&author=Sciacovelli%2CM&author=Nicolli%2CA&author=Ronconi%2CL&author=Fregona%2CD?
- http://scholar.google.com/scholar_lookup?&title=Activation%20of%20mitochondrial%20ERK%20protects%20cancer%20cells%20from%20death%20through%20inhibition%20of%20the%20permeability%20transition&journal=Proc%20Natl%20Acad%20Sci%20USA&volume=107&pages=726-731&publication_year=2010&author=Rasola%2CA&author=Sciacovelli%2CM&author=Chiara%2CF&author=Pantic%2CB&author=Brusilow%2CWS&author=Bernardi%2CP's total income per month
- What's the revenue for http://scholar.google.com/scholar_lookup?&title=Local%20delivery%20of%20PKCepsilon-activating%20peptide%20mimics%20ischemic%20preconditioning%20in%20aged%20hearts%20through%20GSK-3beta%20but%20not%20F1-ATPase%20inactivation&journal=Am%20J%20Physiol%20Heart%20Circ%20Physiol&volume=293&pages=H2056-H2063&publication_year=2007&author=Korzick%2CDH&author=Kostyak%2CJC&author=Hunter%2CJC&author=Saupe%2CKW?
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- http://scholar.google.com/scholar_lookup?&title=Arrangement%20of%20subunits%20in%20intact%20mammalian%20mitochondrial%20ATP%20synthase%20determined%20by%20cryo-EM&journal=Proc%20Natl%20Acad%20Sci%20USA&volume=109&pages=11675-11680&publication_year=2012&author=Baker%2CLA&author=Watt%2CIN&author=Runswick%2CMJ&author=Walker%2CJE&author=Rubinstein%2CJL's financial summary
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