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

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, we utilize isobaric quantitative protein interaction reporter technology (iqPIR) 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 544 statistically significant cross-linked peptide pairs altered in 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 live 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

SUBMITTER: Xiaoting Tang

LAB HEAD: James Edward Bruce

PROVIDER: PXD027757 | Pride | 2022-08-02

REPOSITORIES: Pride

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			Action	DRS
	012621_3707RH_TAC_iqPIR_nonmito_F10_mango_4h_1.raw	Raw
	012621_3707RH_TAC_iqPIR_nonmito_F10_mango_4h_2.raw	Raw
	012621_3707RH_TAC_iqPIR_nonmito_F11_14_mango_4h_1.raw	Raw
	012621_3707RH_TAC_iqPIR_nonmito_F11_14_mango_4h_2.raw	Raw
	012621_3707RH_TAC_iqPIR_nonmito_F1_5_DE_2h_1.raw	Raw

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