The effect of calcium on mitochondrial contact sites: a study on isolated rat hearts

Bernaert, I.; Bie, M. De; Ravingerová, Tanya; Ziegelhöffer, A; Belle, H. Van; Jacob, W.

doi:10.1016/0167-4889(94)90297-6

Cited by 35 publications

(17 citation statements)

References 23 publications

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“…Note the (normal) drop in body temperature and activity during the light period in both animals. metabolic activity [14,47,48]. A direct function for mitCK in the assembly of these structures has been suggested by the extensive studies of Wallimann and coworkers [40,15] showing that mitCK-octamers may physically bridge the gap between the mitochondrial inner-and outer membrane.…”

Section: Consequences For Mitochondria and Er Membranesmentioning

confidence: 98%

Cytoarchitectural and metabolic adaptations in muscles with mitochondrial and cytosolic creatine kinase deficiencies

Steeghs¹,

Oerlemans²,

Haan³

et al. 1998

Bioenergetics of the Cell: Quantitative Aspects

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Section: Consequences For Mitochondria and Er Membranesmentioning

confidence: 98%

Cytoarchitectural and metabolic adaptations in muscles with mitochondrial and cytosolic creatine kinase deficiencies

Steeghs¹,

Oerlemans²,

Haan³

et al. 1998

Bioenergetics of the Cell: Quantitative Aspects

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“…7,[10][11][12][13][14][15] The mtCK level is especially high at the contact sites between the inner and the outer mitochondrial membranes. 16,17 Since this protein has a propensity to bridge vesicles made up by internal and external mitochondrial membrane phospholipids, 18 it has been proposed that it could play a role in contact point formation. 12,18 Scanning transmission electron microscopy and X-ray diffraction have provided a picture of the mtCK octamer.…”

Section: Introductionmentioning

confidence: 99%

Interfacial behavior of cytoplasmic and mitochondrial creatine kinase oligomeric states

et al. 2005

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Adsorption to the air/water interface of isoenzymes of creatine kinase was investigated using surface pressure-area isotherms and Brewster angle microscopy (BAM) observations. Octameric mitochondrial creatine kinase (mtCK) exhibits a significant affinity for the air/water interface. Whatever the mode of formation of the interfacial film, i.e., injection of the protein in the subphase or spreading onto the buffer surface, the final arrangement and conformation adopted by mtCK molecules lead to a similar result. In contrast, the dimeric isoenzymes mtCK and cytosolic MMCK do not induce any surface pressure variation. However, when the subphase contains 0.3M NaCl, both isoenzymes adsorb to the interface. When treated with 0.8 or 3M GdnHCl, muscle creatine kinase (MMCK) becomes surface active and occupies a greater surface than mtCK. This result contrasts with previous observations, often derived from monomeric proteins, that their surface activity is increased upon unfolding. It underlines the possible influence exerted by the protein oligomeric state on its interfacial activity. At a subphase pH of 8.8, which corresponds to the pI of octameric mtCK, the profiles of the isotherms obtained with dimeric and octameric states and the resistance to compression of the protein monolayers are significantly affected when compared to those recorded at pH 7.4. These data suggest that the octamer is more hydrophobic than the dimer and may contribute to explaining why octamers bind to the inner mitochondrial membrane while dimers do not.

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“…Thus it is possible that an interaction of the ANT with VDAC in the contact sites greatly enhances the ability of calcium to induce this change in conformation of the ANT. Conversely, it has been shown that calcium can enhance contact site formation [73].…”

Section: Evidence That the Trigger Site For Calcium Is Integral To Thmentioning

confidence: 99%

The Adenine Nucleotide Translocase: A Central Component of the Mitochondrial Permeability Transition Pore and Key Player in Cell Death

Halestrap

Brenner²

2003

CMC

450

329

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In addition to its normal function, the adenine nucleotide translocase (ANT) forms the inner membrane channel of the mitochondrial permeability transition pore (MPTP). Binding of cyclophilin-D (CyP-D) to its matrix surface (probably on Pro 61 on loop 1) facilitates a calcium-triggered conformational change converting it from a specific transporter to a non-specific pore. The voltage dependent anion channel (VDAC) binds to the outer face of the ANT, at contact sites between the inner and outer membranes, and together VDAC, ANT and CyP-D probably represent the minimum MPTP configuration. The evidence for this is critically reviewed as is the structure and molecular mechanism of the carrier in its normal physiological mode. This provides helpful insights into MPTP regulation by adenine nucleotides, membrane potential and ANT ligands such as carboxyatractyloside and bongkrekic acid. Oxidative stress activates the MPTP by glutathione-mediated cross-linking of Cys 159 and Cys 256 on matrixfacing loops of the ANT that inhibits ADP binding and enhances CyP-D binding. Molecular modeling of the loop containing the ADP binding site suggests an arrangement of aspartate and glutamate residues that may provide a calcium binding site. There are other proteins that may bind to the ANT, modulating MPTP opening and hence cell death. These included members of the Bax/Bcl-2 family (both oncoproteins and tumor suppressors) and viral proteins. Vpr from HIV-1 can bind to ANT and convert it into a pro-apoptotic pore, whereas vMIA from cytomegalovirus interacts to inhibit opening. Thus the ANT may provide a molecular link between physiopathological mechanisms of infection and the regulation of MPTP function and so represents a potential therapeutic target.

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The effect of calcium on mitochondrial contact sites: a study on isolated rat hearts

Cited by 35 publications

References 23 publications

Cytoarchitectural and metabolic adaptations in muscles with mitochondrial and cytosolic creatine kinase deficiencies

Cytoarchitectural and metabolic adaptations in muscles with mitochondrial and cytosolic creatine kinase deficiencies

Interfacial behavior of cytoplasmic and mitochondrial creatine kinase oligomeric states

The Adenine Nucleotide Translocase: A Central Component of the Mitochondrial Permeability Transition Pore and Key Player in Cell Death

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