Mitochondrial a Kinase Anchor Proteins in Cardiovascular Health and Disease: A Review Article on Behalf of the Working Group on Cellular and Molecular Biology of the Heart of the Italian Society of Cardiology

Paolillo, Roberta; D'Apice, S; Schiattarella, Gabriele Giacomo; Ameri, Pietro; Borzacchiello, Domenica; Catalucci, Daniele; Chimenti, Cristina; Crotti, Lia; Sciarretta, Sebastiano; Torella, Daniele; Feliciello, Antonio; Perrino, Cinzia

doi:10.3390/ijms23147691

Cited by 4 publications

(3 citation statements)

References 94 publications

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“…The dual-specificity A-kinase-anchoring protein 2 (D-AKAP2, encoded by the AKAP10 gene) binds protein kinase A (PKA) and is important for the subcellular localization and functionality of PKA, a broad serine/threonine protein kinase that regulates a variety of cellular processes including early development ( Huang et al, 1997 ; Paolillo et al, 2022 ). In humans, the AKAP10 locus has two common alleles defined by an A/G SNP at position 1936 which cause an isoleucine/valine polymorphism at position 646 of the D-AKAP10 protein.…”

Section: Resultsmentioning

confidence: 99%

More evidence for widespread antagonistic pleiotropy in polymorphic disease alleles

Lockwood,

Vo,

Bellafard

et al. 2024

Front. Genet.

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IntroductionMany loci segregate alleles classified as “genetic diseases” due to their deleterious effects on health. However, some disease alleles have been reported to show beneficial effects under certain conditions or in certain populations. The beneficial effects of these antagonistically pleiotropic alleles may explain their continued prevalence, but the degree to which antagonistic pleiotropy is common or rare is unresolved. We surveyed the medical literature to identify examples of antagonistic pleiotropy to help determine whether antagonistic pleiotropy appears to be rare or common.ResultsWe identified ten examples of loci with polymorphisms for which the presence of antagonistic pleiotropy is well supported by detailed genetic or epidemiological information in humans. One additional locus was identified for which the supporting evidence comes from animal studies. These examples complement over 20 others reported in other reviews.DiscussionThe existence of more than 30 identified antagonistically pleiotropic human disease alleles suggests that this phenomenon may be widespread. This poses important implications for both our understanding of human evolutionary genetics and our approaches to clinical treatment and disease prevention, especially therapies based on genetic modification.

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Section: Resultsmentioning

confidence: 99%

More evidence for widespread antagonistic pleiotropy in polymorphic disease alleles

Lockwood,

Vo,

Bellafard

et al. 2024

Front. Genet.

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“…Higher eukaryotes have a variety of A-kinase anchoring proteins (AKAPs) that bind the regulatory subunit to control the PKA’s subcellular localization [ 135 ]. AKAPs have tissue-specific expression and regulate PKA–substrate interactions [ 135 , 136 , 137 , 138 , 139 , 140 ]. They have also been described to form signalosomes, which produce micro-environments of PKA, PKA substrates, PDEs, and/or other upstream components of the PKA pathway [ 141 , 142 ].…”

Section: Key Regulators That Govern Physiological Pathways Rewired Fo...mentioning

confidence: 99%

Advances in S. cerevisiae Engineering for Xylose Fermentation and Biofuel Production: Balancing Growth, Metabolism, and Defense

Wagner

Gasch

2023

JoF

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Genetically engineering microorganisms to produce chemicals has changed the industrialized world. The budding yeast Saccharomyces cerevisiae is frequently used in industry due to its genetic tractability and unique metabolic capabilities. S. cerevisiae has been engineered to produce novel compounds from diverse sugars found in lignocellulosic biomass, including pentose sugars, like xylose, not recognized by the organism. Engineering high flux toward novel compounds has proved to be more challenging than anticipated since simply introducing pathway components is often not enough. Several studies show that the rewiring of upstream signaling is required to direct products toward pathways of interest, but doing so can diminish stress tolerance, which is important in industrial conditions. As an example of these challenges, we reviewed S. cerevisiae engineering efforts, enabling anaerobic xylose fermentation as a model system and showcasing the regulatory interplay’s controlling growth, metabolism, and stress defense. Enabling xylose fermentation in S. cerevisiae requires the introduction of several key metabolic enzymes but also regulatory rewiring of three signaling pathways at the intersection of the growth and stress defense responses: the RAS/PKA, Snf1, and high osmolarity glycerol (HOG) pathways. The current studies reviewed here suggest the modulation of global signaling pathways should be adopted into biorefinery microbial engineering pipelines to increase efficient product yields.

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“…3 Mitochondrial homeostasis is ensured by different mechanisms including biogenesis, mitochondrial dynamics (fusion and fission) and mitophagy (Figure 1). [4][5][6] Mitochondria undergo coordinated cycles of fusion and fission under basal conditions or in response to mitochondrial stress, such as changes of mitochondrial membrane potential (ΔΨm) or nutrient and oxygen depletion. 5 Generally, fusion is activated in the presence of reversible mitochondrial damage, while mitochondrial fission occurs when irreversibly damaged mitochondria accumulate.…”

Section: Introductionmentioning

confidence: 99%

Mitophagy modulation for the treatment of cardiovascular diseases

Forte,

D'Ambrosio,

Schiattarella

et al. 2024

Eur J Clin Investigation

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BackgroundDefects of mitophagy, the selective form of autophagy for mitochondria, are commonly observed in several cardiovascular diseases and represent the main cause of mitochondrial dysfunction. For this reason, mitophagy has emerged as a novel and potential therapeutic target.MethodsIn this review, we discuss current evidence about the biological significance of mitophagy in relevant preclinical models of cardiac and vascular diseases, such as heart failure, ischemia/reperfusion injury, metabolic cardiomyopathy and atherosclerosis.ResultsMultiple studies have shown that cardiac and vascular mitophagy is an adaptive mechanism in response to stress, contributing to cardiovascular homeostasis. Mitophagy defects lead to cell death, ultimately impairing cardiac and vascular function, whereas restoration of mitophagy by specific compounds delays disease progression.ConclusionsDespite previous efforts, the molecular mechanisms underlying mitophagy activation in response to stress are not fully characterized. A comprehensive understanding of different forms of mitophagy active in the cardiovascular system is extremely important for the development of new drugs targeting this process. Human studies evaluating mitophagy abnormalities in patients at high cardiovascular risk also represent a future challenge.

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Mitochondrial a Kinase Anchor Proteins in Cardiovascular Health and Disease: A Review Article on Behalf of the Working Group on Cellular and Molecular Biology of the Heart of the Italian Society of Cardiology

Cited by 4 publications

References 94 publications

More evidence for widespread antagonistic pleiotropy in polymorphic disease alleles

More evidence for widespread antagonistic pleiotropy in polymorphic disease alleles

Advances in S. cerevisiae Engineering for Xylose Fermentation and Biofuel Production: Balancing Growth, Metabolism, and Defense

Mitophagy modulation for the treatment of cardiovascular diseases

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