Proteomic Analysis Suggests Altered Mitochondrial Metabolic Profile Associated with Diabetic Cardiomyopathy

ABSTRACT: Diabetic cardiomyopathy (DbCM) occurs independently of cardiovascular diseases or hypertension, often leading to heart failure and death. To elucidate the molecular mechanisms involved in the DbCM progress, we performed quantitative proteomic profiling analysis in the left ventricle (LV) of leptin receptor‐deficient mice. Six‐month‐old C57BL/6Jlepr/ lepr (db/db) mice exhibited a phenotype of DbCM. By quantitative shotgun proteomic analysis, we identified 53 differentially expressed proteins in db/db mice, mainly associated with energy metabolism. The subunits of ATP synthase that form the F1 domain and Cytochrome c1, a catalytic core subunit of the complex III that is responsible for electron transfer to Cytochrome c, were upregulated in diabetic LVs. Upregulation of these key proteins may represent an adaptive mechanism by the diabetic heart resulting in increased electron transfer and thereby enhancement of mitochondrial ATP production. Conversely, diabetic LVs also showed a decrease in peptide levels of NADH dehydrogenase 1 beta subcomplex subunit 11, a subunit of complex I that catalyzes the transfer of electrons to ubiquinone. Moreover, an atypical kinase COQ8A, an essential lipid‐soluble electron transporter involved in the biosynthesis of ubiquinone, was also downregulated in diabetic LVs. Our study indicates that despite attempts by hearts from the diabetic mice to augment mitochondrial ATP production, decreased levels of key components of the electron transport chain may contribute to impaired mitochondrial ATP production.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

SUBMITTER: Luiz Gustavo de Almeida  

LAB HEAD: Antoine Dufour

PROVIDER: PXD029566 | Pride | 2021-12-02

REPOSITORIES: Pride