scholarly journals A mitochondrial megachannel resides in monomeric F1FO ATP synthase

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Nelli Mnatsakanyan ◽  
Marc C. Llaguno ◽  
Youshan Yang ◽  
Yangyang Yan ◽  
Joachim Weber ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Oligomeric State ◽  
Unilamellar Vesicles ◽  
Mitochondrial Inner Membrane ◽  
Mitochondrial Atp Synthase ◽  
Large Conductance Channel ◽  
Mitochondrial Megachannel

AbstractPurified mitochondrial ATP synthase has been shown to form Ca2+-activated, large conductance channel activity similar to that of mitochondrial megachannel (MMC) or mitochondrial permeability transition pore (mPTP) but the oligomeric state required for channel formation is being debated. We reconstitute purified monomeric ATP synthase from porcine heart mitochondria into small unilamellar vesicles (SUVs) with the lipid composition of mitochondrial inner membrane and analyze its oligomeric state by electron cryomicroscopy. The cryo-EM density map reveals the presence of a single ATP synthase monomer with no density seen for a second molecule tilted at an 86o angle relative to the first. We show that this preparation of SUV-reconstituted ATP synthase monomers, when fused into giant unilamellar vesicles (GUVs), forms voltage-gated and Ca2+-activated channels with the key features of mPTP. Based on our findings we conclude that the ATP synthase monomer is sufficient, and dimer formation is not required, for mPTP activity.

scholarly journals Mitochondrial Inner Membrane Depolarization as a Marker of Platelet Apoptosis

2016 ◽  
Vol 23 (2) ◽  
pp. 139-147 ◽  
Author(s):  
Armen V. Gyulkhandanyan ◽  
David J. Allen ◽  
Sergiy Mykhaylov ◽  
Elena Lyubimov ◽  
Heyu Ni ◽  
...  
Keyword(s):  
Mitochondrial Permeability Transition ◽  
Calcium Ionophore ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Calcium Ionophore A23187 ◽  
Clinical Settings ◽  
Ionophore A23187 ◽  
Platelet Apoptosis ◽  
Mitochondrial Inner Membrane ◽  
Microparticle Formation

Availability of universal marker for the diagnosis of platelet apoptosis is an important but currently unresolved goal of platelet physiology investigations. Mitochondrial inner transmembrane potential (▵Ψm) depolarization is frequently used as a marker of apoptosis in nucleated cells and anucleate platelets. Since ▵Ψm depolarization in platelets is also frequently associated with concurrent induction of other apoptotic responses, it may appear that ▵Ψm depolarization is a good universal marker of platelet apoptosis. However, data presented in the current study indicate that this is incorrect. We report here fundamental differences in the effects of potassium ionophore valinomycin and calcium ionophore A23187 on human platelet apoptosis. Although both A23187-triggered and valinomycin-triggered ▵Ψm depolarization are strongly induced, the former is dependent on the opening of mitochondrial permeability transition pore (MPTP) and the latter is MPTP-independent. Furthermore, effects of calcium and potassium ionophores on other apoptotic events are also basically different. A23187 induces caspase-3 activation, proapoptotic Bax and Bak protein expression, phosphatidylserine exposure, and microparticle formation, whereas valinomycin does not induce these apoptotic manifestations. Discovery of targeted ▵Ψm depolarization not associated with apoptosis in valinomycin-treated platelets indicates that this marker should not be used as a single universal marker of platelet apoptosis in unknown experimental and clinical settings as it may lead to a false-positive apoptosis diagnosis.

scholarly journals FOF1-ATP Synthase Dimers and The Mitochondrial Permeability Transition Pore from Yeast to Mammals

2014 ◽  
Vol 106 (2) ◽  
pp. 3a
Author(s):  
Paolo Bernardi ◽  
Valentina Giorgio ◽  
Michela Carraro ◽  
Sophia von Stockum ◽  
Victoria Burchell ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Mitochondrial Permeability ◽  
Fof1 Atp Synthase

scholarly journals The mitochondrial permeability transition pore activates the mitochondrial unfolded protein response and promotes aging

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Suzanne Angeli ◽  
Anna Foulger ◽  
Manish Chamoli ◽  
Tanuja Harshani Peiris ◽  
Akos Gerencser ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Atp Synthase ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Mitochondrial Permeability ◽  
Unfolded Protein ◽  
Protein Response ◽  
Mitochondrial Unfolded Protein Response

Mitochondrial activity determines aging rate and the onset of chronic diseases. The mitochondrial permeability transition pore (mPTP) is a pathological pore in the inner mitochondrial membrane thought to be composed of the F-ATP synthase (complex V). OSCP, a subunit of F-ATP synthase, helps protect against mPTP formation. How the destabilization of OSCP may contribute to aging, however, is unclear. We have found that loss OSCP in the nematode Caenorhabditis elegans initiates the mPTP and shortens lifespan specifically during adulthood, in part via initiation of the mitochondrial unfolded protein response (UPRmt). Pharmacological or genetic inhibition of the mPTP inhibits the UPRmt and restores normal lifespan. Loss of the putative pore-forming component of F-ATP synthase extends adult lifespan, suggesting that the mPTP normally promotes aging. Our findings reveal how an mPTP/UPRmt nexus may contribute to aging and age-related diseases and how inhibition of the UPRmt may be protective under certain conditions.

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