Mass spectrometry analysis was performed on the purified protein solution of PDHc
Ontology highlight
ABSTRACT:
ORGANISM(S): Sus Scrofa Domesticus
SUBMITTER: 
Yunjie Chang
PROVIDER: PXD059530 | iProX | Wed Jan 08 00:00:00 GMT 2025
REPOSITORIES: iProX
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Project description:Activation of CD4+ T cells requires metabolic reprograming to sustain demands of cellular building blocks and ATP. Pyruvate dehydrogenase kinase (PDK) is an enzyme regulating pyruvate dehydrogenase complex subunit alpha 1 (PDHE1-alpha), which converts pyruvate to acetyl-CoA. Gene expression analysis of TCR-stimulated CD4+ T cells with PDK4 deletion exhibited the reduced calcium signaling and aerobic glycolysis pathway.
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Project description:Cardiac metabolism plays a crucial role in producing sufficient energy to sustain cardiac contractions. However, the role of metabolism in cardiomyocyte proliferation remains unclear. Working with the adult zebrafish heart regeneration model, we first find an increase in the levels of mRNAs encoding enzymes regulating glucose and pyruvate metabolism, including pyruvate kinase M1/2 (Pkm) and pyruvate dehydrogenase kinases (Pdks), specifically in tissues bordering the damaged area. We proceed to show that impaired glycolysis decreases the number of proliferating cardiomyocytes following cardiac injury. These observations are further supported by analyses using loss-of-function models for the metabolic regulators Pkm2a and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Ppargc1a). Cardiomyocyte-specific loss- and gain-of-function manipulations of pyruvate metabolism using Pdk3 and a catalytic subunit of the pyruvate dehydrogenase complex (PDC) reveal its importance in cardiomyocyte dedifferentiation and proliferation. Furthermore, we find that PDK activity can modulate cell cycle progression and protrusive activity in mammalian cardiomyocytes in culture. Our findings reveal new roles for cardiac metabolism and the PDK-PDC axis in cardiomyocyte behavior following cardiac injury.
2020-06-04 | GSE147073 | GEO
Project description:Activation of the pyruvate dehydrogenase complex dictates tumour progression in prostate cancer
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Project description:Cardiac metabolism plays a crucial role in producing sufficient energy to sustain cardiac function. However, the role of metabolism in different aspects of cardiomyocyte regeneration remains unclear. Working with the adult zebrafish heart regeneration model, we first find an increase in the levels of mRNAs encoding enzymes regulating glucose and pyruvate metabolism, including pyruvate kinase M1/2 (Pkm) and pyruvate dehydrogenase kinases (Pdks), especially in tissues bordering the damaged area. We further find that impaired glycolysis decreases the number of proliferating cardiomyocytes following injury. These observations are supported by analyses using loss-of-function models for the metabolic regulators Pkma2 and peroxisome proliferator-activated receptor gamma coactivator 1 alpha. Cardiomyocyte-specific loss- and gain-of-function manipulations of pyruvate metabolism using Pdk3 as well as a catalytic subunit of the pyruvate dehydrogenase complex (PDC) reveal its importance in cardiomyocyte dedifferentiation and proliferation after injury. Furthermore, we find that PDK activity can modulate cell cycle progression and protrusive activity in mammalian cardiomyocytes in culture. Our findings reveal new roles for cardiac metabolism and the PDK-PDC axis in cardiomyocyte behavior following cardiac injury.
2020-07-13 | PXD016235 | Pride
Project description:The proteasome is a vital cellular machine responsible for degrading proteins and maintaining proteostasis. While cryo-EM and cross-linking mass spectrometry (XL-MS) have provided valuable structural insights, these investigations have primarily focused on purified proteasomes in vitro. Here, we perform XL-MS in-situ with an enrichable trifunctional cross-linker to characterize the proteasome within its native cellular environment. Leveraging a two-step enrichment strategy and the high effective protein concentrations within cellular compartments, we generated a comprehensive dataset of proteasome-centered cross-links, which unveiled novel interacting proteins and enabled the construction of dynamic structural models of the proteasome. Furthermore, by resolving nuclear and cytoplasmic fractions, we uncovered distinct proteasome compositions, structural dynamics, and interaction profiles in these two compartments. The cross-linking data also informed AI-based structural predictions and provided crucial restraints for refining docking models. Our integrated approach establishes a powerful workflow for investigating the architecture, functional dynamics, and regulation of large protein complexes in situ, offering deeper insights of their regulatory mechanisms and cellular functions.
2025-08-18 | PXD054983 | JPOST Repository
Project description:Modulation of metabolic flux through pyruvate dehydrogenase complex (PDC) plays an important role in T cell activation and differentiation. PDC sits at the transition between glycolysis and the tricarboxylic acid cycle and is a major producer of acetyl-CoA, marking it as a potential metabolic and epigenetic node. To understand the role of pyruvate dehydrogenase complex in T cell differentiation, we generated mice deficient in T cell pyruvate dehydrogenase E1A (Pdha) subunit using a CD4-cre recombinase-based strategy. Herein, we show that genetic ablation of PDC activity in T cells (TPdh-/-) leads to marked perturbations in glycolysis, the tricarboxylic acid cycle, and OXPHOS. Due to depressed OXPHOS, TPdh-/- T cells became dependent upon substrate level phosphorylation via glycolysis. Due to the block of PDC activity, histone acetylation was reduced, including H3K27, a critical site for CD8+ T cell memory differentiation. Transcriptional and functional profiling revealed abnormal CD8+ memory T cell differentiation in vitro. Collectively, our data indicate that PDC integrates the metabolome and epigenome in memory T cell differentiation. Targeting this metabolic and epigenetic node can have widespread ramifications on cellular function.
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Project description:Modulation of metabolic flux through pyruvate dehydrogenase complex (PDC) plays an important role in T cell activation and differentiation. PDC sits at the transition between glycolysis and the tricarboxylic acid cycle and is a major producer of acetyl-CoA, marking it as a potential metabolic and epigenetic node. To understand the role of pyruvate dehydrogenase complex in T cell differentiation, we generated mice deficient in T cell pyruvate dehydrogenase E1A (Pdha) subunit using a CD4-cre recombinase-based strategy. Herein, we show that genetic ablation of PDC activity in T cells (TPdh-/-) leads to marked perturbations in glycolysis, the tricarboxylic acid cycle, and OXPHOS. Due to depressed OXPHOS, TPdh-/- T cells became dependent upon substrate level phosphorylation via glycolysis. Due to the block of PDC activity, histone acetylation was reduced, including H3K27, a critical site for CD8+ T cell memory differentiation. Transcriptional and functional profiling revealed abnormal CD8+ memory T cell differentiation in vitro. Collectively, our data indicate that PDC integrates the metabolome and epigenome in memory T cell differentiation. Targeting this metabolic and epigenetic node can have widespread ramifications on cellular function.
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Project description:Pyruvate Dehydrogenase Kinase 4 (Pdk4) is a pyruvate dehydrogenase inhibiton gene that strongly regulates metabolism. We studied the expression of Pdk4 in the young and aged mouse heart in both healthy conditions and after ischemic insult.
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