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bioRxiv · 10.1101/2021.08.13.456027

Mitochondrial interactome quantitation reveals structural changes in metabolic machinery in failing murine heart

Caudal, A.·Tang, X.·Chavez, J. D.·Keller, A.·Villet, O.·Zhou, B.·Walker, M. A.·Tian, R.·Bruce, J. E.
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Abstract

Advancements of cross-linking mass spectrometry (XL-MS) for structural analysis of proteins bridges the gap between purified systems and native tissue environments. Here, isobaric quantitative protein interaction reporter technology (iqPIR) was utilized to further extend XL-MS to the first system-wide comparative study of mitochondrial proteins from healthy and diseased murine hearts. The failing heart interactome includes 602 statistically significant cross-linked peptide pairs altered in the disease condition. Structural insight into ketone oxidation metabolons, OXPHOS machinery, and nucleotide transporter hybrid-conformations, support mitochondrial remodeling in failing heart while bringing forth new hypotheses for pathological mechanisms. Application of quantitative cross-linking technology in tissue provides molecular-level insight to complex biological systems difficult to model in cell culture, thus providing a valuable resource for study of human diseases.

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Caudal, A., Tang, X., Chavez, J. D., Keller, A., Villet, O., Zhou, B., Walker, M. A., Tian, R., Bruce, J. E.. 2021-08-14. Mitochondrial interactome quantitation reveals structural changes in metabolic machinery in failing murine heart. https://doi.org/10.1101/2021.08.13.456027

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