Opposing Actions of cGMP and Calcium on the Conductance of the F0 Subunit c Pore

McGeoch, Julie E. M.; McGeoch, Malcolm W.; Mao, Rong; Guidotti, Guido

doi:10.1006/bbrc.2000.3231

Cited by 27 publications

(21 citation statements)

References 17 publications

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“…subunits α and β, which interact with the matrix protein S100A1 154 (not shown in the picture), and the Fo region containing subunit e, which may interact with a hypothetical tropomyosin-like protein localized in the intermembrane space 155 . Ca 2+ -regulatory sites located in the c-ring are also shown 156,157 . Right monomer, the residues (T163, R189, E192, D256) of β subunit interacting with the catalytic metal ions are mapped onto the 3D structure of the bovine F 1 -c-ring complex.…”

Section: Figurementioning

confidence: 92%

“…Another conserved Ca 2+ binding site has been described in the N-terminus of F O subunit c, 156,157 which could also represent a candidate for PTP inhibition by Ca 2+ in the intermembrane space. Ca 2+ binding to subunit c purified from neuronal plasma membrane and reconstituted in artificial membranes was able to block monovalent cation currents 157 , and Ca 2+ binding to subunit c inhibited H + translocation in bacteria and chloroplasts, 158 suggesting that Ca 2+ could alter the c ring conformation.…”

Section: F-atp Synthase and Ptp Formation In The Heartmentioning

confidence: 99%

“…Ca 2+ binding to subunit c purified from neuronal plasma membrane and reconstituted in artificial membranes was able to block monovalent cation currents 157 , and Ca 2+ binding to subunit c inhibited H + translocation in bacteria and chloroplasts, 158 suggesting that Ca 2+ could alter the c ring conformation. However, while the Ca 2+ -binding capacity of subunit c from bacteria and chloroplasts is well established, that of the mammalian subunit c is debated.…”

Section: F-atp Synthase and Ptp Formation In The Heartmentioning

confidence: 99%

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From ATP to PTP and Back

Bernardi

Lisa

Fogolari

et al. 2015

Circulation Research

102

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Mitochondria play a fundamental role in heart physiology, but are also key effectors of dysfunction and death. This dual role assumes a new meaning following recent advances on the nature and regulation of the permeability transition pore, an inner membrane channel whose opening requires matrix Ca2+ and is modulated by many effectors including reactive oxygen species, matrix cyclophilin D, Pi and matrix pH. The recent demonstration that the F-ATP synthase can reversibly undergo a Ca2+-dependent transition to form a channel that mediates the permeability transition opens new perspectives to the field. These findings demand a reassessment of the modifications of F-ATP synthase that take place in the heart under pathological conditions and of their potential role in determining the transition of F-ATP synthase from and energy-conserving into an energy-dissipating device.

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Section: Figurementioning

confidence: 92%

Section: F-atp Synthase and Ptp Formation In The Heartmentioning

confidence: 99%

Section: F-atp Synthase and Ptp Formation In The Heartmentioning

confidence: 99%

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From ATP to PTP and Back

Bernardi

Lisa

Fogolari

et al. 2015

Circulation Research

102

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“…Alternatively, the calcium deposits may originate from lysosome-derived structures, as aberrant lysosomal calcium accumulation due to defects in the lysosomal Trpml1 channel has been described for the related LSDs, Mucolipidosis and Niemann-Pick C 75–77 . This is an attractive possibility, as the lysosomes of Cb Cln6 nclf cerebellar cells are known to accumulate the calcium-regulated 78 subunit c of mitochondrial ATP-synthase 31 , providing a route for enhanced lysosomal calcium entry, whereas defects in Trpml1 may prevent lysosomal calcium extrusion. Although subunit c storage was not evident in subconfluent cultures 31 , it is possible that low levels of increased lysosomal subunit c were below the detection limits in that study.…”

Section: Discussionmentioning

confidence: 99%

X-ray fluorescence imaging reveals subcellular biometal disturbances in a childhood neurodegenerative disorder

Grubman

James

et al. 2014

Chem. Sci.

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Biometals such as zinc, iron, copper and calcium play key roles in diverse physiological processes in the brain, but can be toxic in excess. A hallmark of neurodegeneration is a failure of homeostatic mechanisms controlling the concentration and distribution of these elements, resulting in overload, deficiency or mislocalization. A major roadblock to understanding the impact of altered biometal homeostasis in neurodegenerative disease is the lack of rapid, specific and sensitive techniques capable of providing quantitative subcellular information on biometal homeostasis in situ. Recent advances in X-ray fluorescence detectors have provided an opportunity to rapidly measure biometal content at subcellular resolution in cell populations using X-ray Fluorescence Microscopy (XFM). We applied this approach to investigate subcellular biometal homeostasis in a cerebellar cell line isolated from a natural mouse model of a childhood neurodegenerative disorder, the CLN6 form of neuronal ceroid lipofuscinosis, commonly known as Batten disease. Despite no global changes to whole cell concentrations of zinc or calcium, XFM revealed significant subcellular mislocalization of these important biological second messengers in cerebellar Cln6nclf (CbCln6nclf) cells. XFM revealed that nuclear-to-cytoplasmic trafficking of zinc was severely perturbed in diseased cells and the subcellular distribution of calcium was drastically altered in CbCln6nclf cells. Subtle differences in the zinc K-edge X-ray Absorption Near Edge Structure (XANES) spectra of control and CbCln6nclf cells suggested that impaired zinc homeostasis may be associated with an altered ligand set in CbCln6nclf cells. Importantly, a zinc-complex, ZnII(atsm), restored the nuclear-to-cytoplasmic zinc ratios in CbCln6nclf cells via nuclear zinc delivery, and restored the relationship between subcellular zinc and calcium levels to that observed in healthy control cells. ZnII(atsm) treatment also resulted in a reduction in the number of calcium-rich puncta observed in CbCln6nclf cells. This study highlights the complementarities of bulk and single cell analysis of metal content for understanding disease states. We demonstrate the utility and broad applicability of XFM for subcellular analysis of perturbed biometal metabolism and mechanism of action studies for novel therapeutics to target neurodegeneration.

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“…Second, McGeoch et al reported that the c-subunit current was extremely sensitive to inhibition by Ca 2+ (Figure 1A), demonstrating the closure of subunit c pores due to the cooperative effect of at least four Ca 2+ ions per ring (7). In contrast, Alavian et al showed that the current mediated by reconstituted c subunits in lipid bilayers is not sensitive to Ca 2+ , and it is induced by Ca 2+ when measured in submitochondrial vesicles (1), as expected by the PTP (9).…”

mentioning

confidence: 97%