Rosca 2011 Biochim Biophys Acta

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Rosca M, Minkler P, Hoppel CL (2011) Cardiac mitochondria in heart failure: Normal cardiolipin profile and increased threonine phosphorylation of Complex IV. Biochim Biophys Acta 1807:1373-82.

» PMID: 21320465 Open Access

Rosca M, Minkler P, Hoppel CL (2011) Biochim Biophys Acta

Abstract: Mitochondrial dysfunction is a major contributor in heart failure (HF).We investigated whether the decrease in respirasome organization reported by us previously in cardiac mitochondria in HF is due to changes in the phospholipids of themitochondrial innermembrane ormodifications of the subunits of the electron transport chain (ETC) complexes. The contents of the main phospholipid species, including cardiolipin, as well as the molecular species of cardiolipin were unchanged in cardiac mitochondria in HF. Oxidized cardiolipin molecular species were not observed. In heart mitochondria isolated from HF, Complex IV not incorporated into respirasomes exhibits increased threonine phosphorylation. Since HF is associated with increased adrenergic drive to cardiomyocytes, this increased protein phosphorylation might be explained by the involvement of cAMP-activated protein kinase. Does the preservation of cAMP-induced phosphorylation changes of mitochondrial proteins or the addition of exogenous cAMP have similar effects on oxidative phosphorylation? The usage of phosphatase inhibitors revealed a specific decrease in complex I-supported respiration with glutamate. In saponin-permeabilized cardiac fibers, pre-incubation with cAMP decreases oxidative phosphorylation due to a defect localized at Complex IV of the ETC inter alia. We propose that phosphorylation of specific Complex IV subunits decreases oxidative phosphorylation either by limiting the incorporation of Complex IV in supercomplexes or by decreasing supercomplex stability.

Keywords: Mitochondria, Supercomplex, Oxidative phosphorylation, Cardiolipin, Protein threonine phosphorylation

O2k-Network Lab: US OH Cleveland Hoppel CL


Labels: MiParea: Comparative MiP;environmental MiP 

Stress:Ischemia-reperfusion  Organism: Rat, Dog  Tissue;cell: Heart  Preparation: Permeabilized tissue, Isolated mitochondria  Enzyme: Complex IV;cytochrome c oxidase 


HRR: Oxygraph-2k 

heart failure, dog