The physics of normal and impaired mitochondrial electron transfer

ORAL

Abstract

The mitochondrial electron transport chain (ETC) produces most of our bodies’ energy in the form of ATP. Within the ETC, complex II, also known as succinate dehydrogenase (SDH), plays a unique role in that it converts succinate to fumarate as part of the Krebs cycle while simultaneously feeding energetic electrons to the ETC. The electrons travel along a chain of three Fe-S clusters in subunit B (SDHB) before entering the membranous domain containing a heme group and ubiquinone, which ultimately transports them to complex III. Some SDHB mutations in the form of amino acid replacements trigger aggressive growth of certain cancers, such as paraganglioma and pheochromocytoma. We will discuss our collaborative experimental and theoretical program, which includes measurements of human tissue and cell lines, and calculations of normal and mutated electron tunneling rates using Marcus theory. Our preliminary results suggest that some mutations disrupt SDHB electron pathways, causing many electrons to fail to reach their ubiquinone target and instead spill out to generate reactive oxygen species that increase tumorigenicity.

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Presenters

  • Pavithi Weerasinghe

    • Dept. of Physics and Texas Center for Superconductivity, University of Houston
    • Department of Physics and Texas Center for Superconductivity, University of Houston

Authors

  • Pavithi Weerasinghe

    • Dept. of Physics and Texas Center for Superconductivity, University of Houston
    • Department of Physics and Texas Center for Superconductivity, University of Houston

  • Martha Villagran

    • Dept. of Physics and Texas Center for Superconductivity, University of Houston
    • Department of Physics and Texas Center for Superconductivity, University of Houston

  • Aijun Zhang

    • Center for Bioenergetics, Houston Methodist Research Institute

  • Dale J Hamilton

    • Center for Bioenergetics, Houston Methodist Research Institute

  • Brian J Miles

    • Department of Urology, Houston Methodist

  • Jarek Wosik

    • Electrical and Computer Engineering Department, University of Houston
    • Department of Electrical and Computer Engineering and Texas Center for Superconductivity, University of Houston

  • John H Miller

    • Dept. of Physics and Texas Center for Superconductivity, University of Houston
    • Department of Physics and Texas Center for Superconductivity, University of Houston