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Summary Acyl CoA metabolites derived from the catabolism of carbon fuels can react with lysine residues of mitochondrial proteins, giving rise to a large family of post-translational modifications (PTMs). Mass spectrometry-based detection of thousands of acyl-PTMs scattered throughout the proteome has established a strong link between mitochondrial hyperacylation and cardiometabolic diseases; however, the functional consequences of these modifications remain uncertain. Here, we use a comprehensive respiratory diagnostics platform to evaluate three disparate models of mitochondrial hyperacylation in the mouse heart caused by genetic deletion of malonyl CoA decarboxylase (MCD), SIRT5 demalonylase and desuccinylase, or SIRT3 deacetylase. In each case, elevated acylation is accompanied by marginal respiratory phenotypes. Of the >60 mitochondrial energy fluxes evaluated, the only outcome consistently observed across models is a ∼15% decrease in ATP synthase activity. In sum, the findings suggest that the vast majority of mitochondrial acyl PTMs occur as stochastic events that minimally affect mitochondrial bioenergetics. Graphical Abstract Highlights • Interrogating the role of lysine acylation in regulating mitochondrial quality • Comparison of three disparate genetic models of hyperacylated heart mitochondria • A mitochondrial diagnostics platform evaluates >60 distinct energetic fluxes • Substantial shifts in the acyl-lysine landscape minimally affect bioenergetics Fisher-Wellman et al. use a recently developed mitochondrial diagnostics platform for deep phenotyping of heart mitochondria derived from three disparate genetic models of protein hyperacylation. Their findings oppose the notion that hyperacylation of the mitochondrial proteome leads to broad-ranging vulnerabilities in respiratory function and bioenergetics. [ABSTRACT FROM AUTHOR]

The article reviews the exhibition "Sculpture Victorious" at the Yale Center for British Art in New Haven, Connecticut from September 11, 2014 to November 30, 2014 and at the Tate Britain museum in London, England from February 25, 2015 to May 25, 2015.

The article questions Graham Pollard's theory that the owner of a house in Florence near the Duomo, Italy belongs to Paduan sculptor Andrea Briosco, called Riccio, and not Michaelangelo Tanaglia who declared himself as the owner of the house. According to the author, the first theory is the absence of Florentine character in Riccio's earliest work. The author adds that the traditional date of Riccio's birth around 1470 is supported by Paduan data that a 10-year-old Paduan cannot easily be supposed to have had a house of his own in Florence. He supports the second theory of Pollard because exposure to Florentine art could help explain the total mastery exhibited in Riccio's first great independent works, the two historiated reliefs for the choir of the Santo.

In a letter to the editor, the author comments on a discovery of a painting by or after the Italian sixteenth-century artist Francesco Salviati which includes a depiction of a statue of Cupid attributed to Michelangelo currently housed at the Metropolitan Museum of Art in New York City.

The article presents an explanation for the publication of the catalogue "The Jack and Belle Linsky Collection in the Metropolitan Museum of Art," which coincided withe opening of the Linsky galleries in the Metropolitan Museum in 1984. While the catalogue included 373 works of art, Belle Linsky relinquished her life interest in fourteen objects in 1985. The "Metropolitan Museum Journal" decided to allow the description of these additional objects as a sequel to the 1984 catalogue, based on the style and arrangement of that publication.

Plants tolerate large variations in the intensity of the light environment by controlling the efficiency of solar to chemical energy conversion. To do this, plants have a mechanism to detect the intensity, duration, and change in light as they experience moving shadows, flickering light, and cloud cover. Sugars are the primary products of CO 2 fixation, a metabolic pathway that is rate limited by this solar energy conversion. We propose that sugar is a signal encoding information about the intensity, duration and change in the light environment. We previously showed that the Arabidopsis heterotrimeric G protein complex including its receptor-like Regulator of G signaling protein, AtRGS1, detects both the concentration and the exposure time of sugars (Fu et al., 2014. Cell 156: 1084–1095). This unique property, designated dose-duration reciprocity, is a behavior that emerges from the system architecture / system motif. Here, we show that another property of the signaling system is to detect large changes in light while at the same time, filtering types of fluctuation in light that do not affect photosynthesis efficiency. When AtRGS1 is genetically ablated, photosynthesis efficiency is reduced in a changing- but not a constant-light environment. Mathematical modeling revealed that information about changes in the light environment is encoded in the amount of free AtRGS1 that becomes compartmentalized following stimulation. We propose that this property determines when to adjust photosynthetic efficiency in an environment where light intensity changes abruptly caused by moving shadows on top of a background of light changing gradually from sun rise to sun set and fluctuating light such as that caused by fluttering leaves. [ABSTRACT FROM AUTHOR]

Nicotinamide riboside supplements (NRS) have been touted as a nutraceutical that promotes cardiometabolic and musculoskeletal health by enhancing nicotinamide adenine dinucleotide (NAD + ) biosynthesis, mitochondrial function, and/or the activities of NAD-dependent sirtuin deacetylase enzymes. This investigation examined the impact of NRS on whole body energy homeostasis, skeletal muscle mitochondrial function, and corresponding shifts in the acetyl-lysine proteome, in the context of diet-induced obesity using C57BL/6NJ mice. The study also included a genetically modified mouse model that imposes greater demand on sirtuin flux and associated NAD + consumption, specifically within muscle tissues. In general, whole body glucose control was marginally improved by NRS when administered at the midpoint of a chronic high-fat diet, but not when given as a preventative therapy upon initiation of the diet. Contrary to anticipated outcomes, the study produced little evidence that NRS increases tissue NAD + levels, augments mitochondrial function, and/or mitigates diet-induced hyperacetylation of the skeletal muscle proteome., Competing Interests: The authors received NR Chloride as a gift from ChromaDex Inc., (© 2021 The Authors.)

Caloric restriction (CR) can prolong aged skeletal muscle function, yet the molecular mechanisms are not completely understood. We performed phosphoproteomic analysis on muscle from young and old mice fed an ad libitum diet, and old mice fed a CR diet. CR promoted a youthful phosphoproteomic signature, suppressing several known "pro-aging" pathways including Protein kinase A (PKA). This study validates global signaling changes in skeletal muscle during CR., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

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.

This study sought to examine the functional significance of mitochondrial protein acetylation using a double knockout (DKO) mouse model harboring muscle-specific deficits in acetyl-CoA buffering and lysine deacetylation, due to genetic ablation of carnitine acetyltransferase and Sirtuin 3, respectively. DKO mice are highly susceptible to extreme hyperacetylation of the mitochondrial proteome and develop a more severe form of diet-induced insulin resistance than either single KO mouse line. However, the functional phenotype of hyperacetylated DKO mitochondria is largely normal. Of the >120 measures of respiratory function assayed, the most consistently observed traits of a markedly heightened acetyl-lysine landscape are enhanced oxygen flux in the context of fatty acid fuel and elevated rates of electron leak. In sum, the findings challenge the notion that lysine acetylation causes broad-ranging damage to mitochondrial quality and performance and raise the possibility that acetyl-lysine turnover, rather than acetyl-lysine stoichiometry, modulates redox balance and carbon flux., (Copyright © 2019 Elsevier Inc. All rights reserved.)