Extreme Acetylation of the Cardiac Mitochondrial Proteome Does Not Promote Heart Failure

Rationale: Circumstantial evidence links the development of heart failure to posttranslational modifications of mitochondrial proteins, including lysine acetylation (Kac). Nonetheless, direct evidence that Kac compromises mitochondrial performance remains sparse. Objective: This study sought to explore the premise that mitochondrial Kac contributes to heart failure by disrupting oxidative metabolism. Methods and Results: A DKO (dual knockout) mouse line with deficiencies in CrAT (carnitine acetyltransferase) and Sirt3 (sirtuin 3)—enzymes that oppose Kac by buffering the acetyl group pool and catalyzing lysine deacetylation, respectively—was developed to model extreme mitochondrial Kac in cardiac muscle, as confirmed by quantitative acetyl-proteomics. The resulting impact on mitochondrial bioenergetics was evaluated using a respiratory diagnostics platform that permits comprehensive assessment of mitochondrial function and energy transduction. Susceptibility of DKO mice to heart failure was investigated using transaortic constriction as a model of cardiac pressure overload. The mitochondrial acetyl-lysine landscape of DKO hearts was elevated well beyond that observed in response to pressure overload or Sirt3 deficiency alone. Relative changes in the abundance of specific acetylated lysine peptides measured in DKO versus Sirt3 KO hearts were strongly correlated. A proteomics comparison across multiple settings of hyperacetylation revealed ≈86% overlap between the populations of Kac peptides affected by the DKO manipulation as compared with experimental heart failure. Despite the severity of cardiac Kac in DKO mice relative to other conditions, deep phenotyping of mitochondrial function revealed a surprisingly normal bioenergetics profile. Thus, of the >120 mitochondrial energy fluxes evaluated, including substrate-specific dehydrogenase activities, respiratory responses, redox charge, mitochondrial membrane potential, and electron leak, we found minimal evidence of oxidative insufficiencies. Similarly, DKO hearts were not more vulnerable to dysfunction caused by transaortic constriction–induced pressure overload. Conclusions: The findings challenge the premise that hyperacetylation per se threatens metabolic resilience in the myocardium by causing broad-ranging disruption to mitochondrial oxidative machinery.

Mutually-dependent kinetics and energetics of photocatalyst/co-catalyst/two-redox liquid junctions

We elucidate the multi-redox charge-transfer kinetics across a photocatalyst/(co-catalyst)/water interface and reveal the dynamic interplay between local energetics and kinetics.

Aromatic character of [Au13]5+ and [MAu12]4+/6+ (M = Pd, Pt) cores in ligand protected gold nanoclusters – interplay between spherical and planar σ-aromatics

Ligand-protected superatoms are able to behave as both spherical and planar aromatic species, providing a strong link between spherical and planar σ-aromatics, which can be controlled selectively by tuning their redox charge states.

Cyclic voltammetry modeling of proton transport effects on redox charge storage in conductive materials: application to a TiO2 mesoporous film

Cyclic voltammetry is a particularly useful tool for characterizing proton transport in conductive materials.

Voltammetry of Suspensions of Polyaniline-coated Graphene Composites

Flaky particles of polyaniline (PANI)-graphene (GN) with rectangular size of 1.0-1.5 mm are dispersed in aqueous solution so that their suspension is stable for one day without aggregation. The weight fraction of PANI in the particle is 75 %, which is independent of the loaded fraction of PANI in the synthesis. The PANI-GN film made of the suspension forms a self-standing, elastic, conductive film. The PANI-GN suspension exhibits both the reduction and the oxidation waves at potentials similar to those of PANI adsorbed on an electrode, whereas the PANI-GO suspension shows only the voltammetric reduction wave. The redox peak currents are controlled by diffusion of PANI-GN flakes. The PANI-GN film cast on the electrode shows voltammetric peaks for PANI, of which redox charge is larger than that of the electrochemically polymerized PANI film with the common weight of PANI. This fact can be explained in terms of the electrochemically exhaustive oxidation of PANI through the electric conduction of GN.