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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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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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- How profitable is http://scholar.google.com/scholar_lookup?&title=Mitochondrial%20apoptosis%20without%20VDAC&journal=Nat%20Cell%20Biol&volume=9&pages=487-489&publication_year=2007&author=Galluzzi%2CL&author=Kroemer%2CG?
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- How much does http://scholar.google.com/scholar_lookup?&title=A%20fourth%20ADP%2FATP%20carrier%20isoform%20in%20man%3A%20identification%2C%20bacterial%20expression%2C%20functional%20characterization%20and%20tissue%20distribution&journal=FEBS%20Lett&volume=579&pages=633-637&publication_year=2005&author=Dolce%2CV&author=Scarcia%2CP&author=Iacopetta%2CD&author=Palmieri%2CF pull in?
- What's the profit of http://scholar.google.com/scholar_lookup?&title=Adenine%20nucleotide%20translocase%203%20%28ANT3%29%20overexpression%20induces%20apoptosis%20in%20cultured%20cells&journal=FEBS%20Lett&volume=563&pages=155-160&publication_year=2004&author=Zamora%2CM&author=Granell%2CM&author=Mampel%2CT&author=Vinas%2CO?
- Check the income stats for http://scholar.google.com/scholar_lookup?&title=VDAC2%20inhibits%20BAK%20activation%20and%20mitochondrial%20apoptosis&journal=Science&volume=301&pages=513-517&publication_year=2003&author=Cheng%2CEH&author=Sheiko%2CTV&author=Fisher%2CJK&author=Craigen%2CWJ&author=Korsmeyer%2CSJ
- How much revenue does http://scholar.google.com/scholar_lookup?&title=Bid-induced%20conformational%20change%20of%20Bax%20is%20responsible%20for%20mitochondrial%20cytochrome%20c%20release%20during%20apoptosis&journal=J%20Cell%20Biol&volume=144&pages=891-901&publication_year=1999&author=Desagher%2CS&author=Osen-Sand%2CA&author=Nichols%2CA&author=Eskes%2CR&author=Montessuit%2CS&author=Lauper%2CS bring in?
- Check the income stats for http://scholar.google.com/scholar_lookup?&title=Osmotic%20reversal%20of%20phosphate-induced%20mitochondrial%20swelling&journal=Biochim%20Biophys%20Acta&volume=104&pages=612-615&publication_year=1965&author=Tedeschi%2CH&author=Hegarty%2CHJ&author=James%2CJM
- Profit of http://scholar.google.com/scholar_lookup?&title=The%20mitochondrial%20transporter%20family%20%28SLC25%29%3A%20physiological%20and%20pathological%20implications&journal=Pflugers%20Arch&volume=447&pages=689-709&publication_year=2004&author=Palmieri%2CF
- How much does http://scholar.google.com/scholar_lookup?&title=Permeability%20transition%20in%20rat%20liver%20mitochondria%20is%20modulated%20by%20the%20ATP-Mg%2FPi%20carrier&journal=Am%20J%20Physiol%20Gastrointest%20Liver%20Physiol&volume=285&pages=G274-G281&publication_year=2003&author=Hagen%2CT&author=Lagace%2CCJ&author=Modica-Napolitano%2CJS&author=Aprille%2CJR generate monthly?
- What's http://scholar.google.com/scholar_lookup?&title=SCaMC-1%20promotes%20cancer%20cell%20survival%20by%20desensitizing%20mitochondrial%20permeability%20transition%20via%20ATP%2FADP-mediated%20matrix%20Ca%282%2B%29%20buffering&journal=Cell%20Death%20Differ&volume=19&pages=650-660&publication_year=2012&author=Traba%2CJ&author=Del%20Arco%2CA&author=Duchen%2CMR&author=Szabadkai%2CG&author=Satrustegui%2CJ's gross income?
- How much does http://scholar.google.com/scholar_lookup?&title=Cytopathic%20effects%20of%20the%20cytomegalovirus-encoded%20apoptosis%20inhibitory%20protein%20vMIA&journal=J%20Cell%20Biol&volume=174&pages=985-996&publication_year=2006&author=Poncet%2CD&author=Pauleau%2CAL&author=Szabadkai%2CG&author=Vozza%2CA&author=Scholz%2CSR&author=Le%20Bras%2CM net monthly?
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- How much money does 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 generate?
- Profit of 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
- What are the total 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 are the earnings of 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?
- How much does http://scholar.google.com/scholar_lookup?&title=Unexpected%20role%20of%20the%20phosphate%20carrier%20in%20mitochondrial%20fragmentation&journal=Cell%20Death%20Differ&volume=15&pages=616-618&publication_year=2008&author=Pauleau%2CAL&author=Galluzzi%2CL&author=Scholz%2CSR&author=Larochette%2CN&author=Kepp%2CO&author=Kroemer%2CG generate monthly?
- What's the revenue for 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?
- Get to know what's the income of 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
- See how much 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 makes per month
- How much income does 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 have?
- 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 revenue does 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 generate?
- What's http://scholar.google.com/scholar_lookup?&title=PK11195%2C%20a%20specific%20ligand%20of%20the%20peripheral%20benzodiazepine%20receptor%2C%20may%20protect%20pancreatic%20beta-cells%20from%20cytokine-induced%20cell%20death&journal=Artif%20Cells%20Blood%20Substit%20Immobil%20Biotechnol&volume=40&pages=56-61&publication_year=2012&author=Klaffschenkel%2CRA&author=Waidmann%2CM&author=Northoff%2CH&author=Mahmoud%2CAA&author=Lembert%2CN's gross income?
- What's the financial gain of http://scholar.google.com/scholar_lookup?&title=Ligands%20of%20the%20mitochondrial%2018%E2%80%89kDa%20translocator%20protein%20attenuate%20apoptosis%20of%20human%20glioblastoma%20cells%20exposed%20to%20erucylphosphohomocholine&journal=Cell%20Oncol&volume=30&pages=435-450&publication_year=2008&author=Kugler%2CW&author=Veenman%2CL&author=Shandalov%2CY&author=Leschiner%2CS&author=Spanier%2CI&author=Lakomek%2CM?
- See how much http://scholar.google.com/scholar_lookup?&title=The%20nitric%20oxide%20donor%20sodium%20nitroprusside%20requires%20the%2018%E2%80%89kDa%20Translocator%20Protein%20to%20induce%20cell%20death&journal=Apoptosis&volume=17&pages=647-665&publication_year=2012&author=Shargorodsky%2CL&author=Veenman%2CL&author=Caballero%2CB&author=Pe%27er%2CY&author=Leschiner%2CS&author=Bode%2CJ makes per month
- What's the total monthly financial gain of http://scholar.google.com/scholar_lookup?&title=Modulation%20of%20intracellular%20Ca2%2B%20signalling%20in%20HeLa%20cells%20by%20the%20apoptotic%20cell%20death%20enhancer%20PK11195&journal=Biochem%20Pharmacol&volume=76&pages=1628-1636&publication_year=2008&author=Campanella%2CM&author=Szabadkai%2CG&author=Rizzuto%2CR?
- How much 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 rake in every month?
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- How much does http://scholar.google.com/scholar_lookup?&title=Some%20new%20aspects%20of%20creatine%20kinase%20%28CK%29%3A%20compartmentation%2C%20structure%2C%20function%20and%20regulation%20for%20cellular%20and%20mitochondrial%20bioenergetics%20and%20physiology&journal=Biofactors&volume=8&pages=229-234&publication_year=1998&author=Wallimann%2CT&author=Dolder%2CM&author=Schlattner%2CU&author=Eder%2CM&author=Hornemann%2CT&author=O%27Gorman%2CE pull in monthly?
- What's the income of 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?
- How much does 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 bring in each month?
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- How much revenue does http://scholar.google.com/scholar_lookup?&title=Hexokinase%20II%3A%20the%20integration%20of%20energy%20metabolism%20and%20control%20of%20apoptosis&journal=Curr%20Med%20Chem&volume=10&pages=1535-1551&publication_year=2003&author=Pastorino%2CJG&author=Hoek%2CJB bring in?
- How much 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 pull in?
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- What's the financial intake of http://scholar.google.com/scholar_lookup?&title=Voltage-dependent%20anion%20channel%201-based%20peptides%20interact%20with%20hexokinase%20to%20prevent%20its%20anti-apoptotic%20activity&journal=J%20Biol%20Chem&volume=284&pages=3946-3955&publication_year=2009&author=Arzoine%2CL&author=Zilberberg%2CN&author=Ben-Romano%2CR&author=Shoshan-Barmatz%2CV?
- How much money does http://scholar.google.com/scholar_lookup?&title=Disruption%20of%20hexokinase%20II-mitochondrial%20binding%20blocks%20ischemic%20preconditioning%20and%20causes%20rapid%20cardiac%20necrosis&journal=Circ%20Res&volume=108&pages=1165-1169&publication_year=2011&author=Smeele%2CKM&author=Southworth%2CR&author=Wu%2CR&author=Xie%2CC&author=Nederlof%2CR&author=Warley%2CA make?
- What's the total monthly financial gain of http://scholar.google.com/scholar_lookup?&title=Metabolic%20targets%20for%20cancer%20therapy&journal=Nat%20Rev%20Drug%20Discov&volume=12&pages=829-846&publication_year=2013&author=Galluzzi%2CL&author=Kepp%2CO&author=Vander%20Heiden%2CMG&author=Kroemer%2CG?
- Income figures for http://scholar.google.com/scholar_lookup?&title=Glucose%20phosphorylation%20and%20mitochondrial%20binding%20are%20required%20for%20the%20protective%20effects%20of%20hexokinases%20I%20and%20II&journal=Mol%20Cell%20Biol&volume=28&pages=1007-1017&publication_year=2008&author=Sun%2CL&author=Shukair%2CS&author=Naik%2CTJ&author=Moazed%2CF&author=Ardehali%2CH
- How much revenue does http://scholar.google.com/scholar_lookup?&title=Hexokinase%20II%20detachment%20from%20mitochondria%20triggers%20apoptosis%20through%20the%20permeability%20transition%20pore%20independent%20of%20voltage-dependent%20anion%20channels&journal=PLoS%20ONE&volume=3&publication_year=2008&author=Chiara%2CF&author=Castellaro%2CD&author=Marin%2CO&author=Petronilli%2CV&author=Brusilow%2CWS&author=Juhaszova%2CM produce monthly?
- http://scholar.google.com/scholar_lookup?&title=Hexokinase%201%20blocks%20apoptotic%20signals%20at%20the%20mitochondria&journal=Cell%20Signal&volume=25&pages=2685-2692&publication_year=2013&author=Schindler%2CA&author=Foley%2CE's total income per month
- How much revenue does 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 generate?
- What's the financial intake of http://scholar.google.com/scholar_lookup?&title=Protein%20kinase%20Cepsilon%20interacts%20with%20and%20inhibits%20the%20permeability%20transition%20pore%20in%20cardiac%20mitochondria&journal=Circ%20Res&volume=92&pages=873-880&publication_year=2003&author=Baines%2CCP&author=Song%2CCX&author=Zheng%2CYT&author=Wang%2CGW&author=Zhang%2CJ&author=Wang%2COL?
- What's 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's gross income?
- How much does 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 pull in?
- Discover the revenue of 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
- What's the financial gain 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?
- How much does 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 generate monthly?
- How much profit does 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 make?
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