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Characterization of Myelin Sheath FoF1-ATP Synthase and its Regulation by IF1

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Abstract

FoF1-ATP synthase is the nanomotor responsible for most of ATP synthesis in the cell. In physiological conditions, it carries out ATP synthesis thanks to a proton gradient generated by the respiratory chain in the inner mitochondrial membrane. We previously reported that isolated myelin vesicles (IMV) contain functional FoF1-ATP synthase and respiratory chain complexes and are able to conduct an aerobic metabolism, to support the axonal energy demand. In this study, by biochemical assay, Western Blot (WB) analysis and immunofluorescence microscopy, we characterized the IMV FoF1-ATP synthase. ATP synthase activity decreased in the presence of the specific inhibitors (olygomicin, DCCD, FCCP, valynomicin/nigericin) and respiratory chain inhibitors (antimycin A, KCN), suggesting a coupling of oxygen consumption and ATP synthesis. ATPase activity was inhibited in low pH conditions. WB and microscopy analyses of both IMV and optic nerves showed that the Inhibitor of F1 (IF1), a small protein that binds the F1 moiety in low pH when of oxygen supply is impaired, is expressed in myelin sheath. Data are discussed in terms of the role of IF1 in the prevention of the reversal of ATP synthase in myelin sheath during central nervous system ischemic events. Overall, data are consistent with an energetic role of myelin sheath, and may shed light on the relationship among demyelination and axonal degeneration.

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Acknowledgment

This study was supported by a Grant from the “Compagnia di San Paolo”- Neuroscience Program, for the research project entitled: “Energetic metabolism in myelinated axon: a new trophic role of myelin sheath”.

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Authors and Affiliations

  1. Biology Department, University of Genova, Viale Benedetto XV 3, 16132, Genoa, Italy

    Silvia Ravera, Isabella Panfoli, Maria Grazia Aluigi, Daniela Calzia & Alessandro Morelli

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  1. Silvia Ravera
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  2. Isabella Panfoli
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  3. Maria Grazia Aluigi
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  4. Daniela Calzia
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  5. Alessandro Morelli
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Correspondence to Alessandro Morelli.

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Silvia Ravera and Isabella Panfoli have contributed equally to this study.

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Ravera, S., Panfoli, I., Aluigi, M.G. et al. Characterization of Myelin Sheath FoF1-ATP Synthase and its Regulation by IF1 . Cell Biochem Biophys 59, 63–70 (2011). https://doi.org/10.1007/s12013-010-9112-1

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