Enzymology of the Nucleus

Siebert, Günther; Humphrey, G. Bennett

doi:10.1002/9780470122723.ch5

Cited by 33 publications

(10 citation statements)

References 139 publications

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“…The first reports of glycolytic enzymes present in the nucleus date to the late 1950s [8][9][10], but all essential glycolytic enzymes have now been observed in the nucleus [11] (Figure 1). Glycolysis produces pyruvate from glucose using the oxidative potential of NAD + [ 2 4 _ T D $ D I F F ] which is converted to NADH.…”

Section: Glycolytic Enzymes In the Nucleusmentioning

confidence: 99%

Metabolic Enzymes Moonlighting in the Nucleus: Metabolic Regulation of Gene Transcription

Boukouris

Zervopoulos

Michelakis

2016

Trends in Biochemical Sciences

243

206

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Section: Glycolytic Enzymes In the Nucleusmentioning

confidence: 99%

Metabolic Enzymes Moonlighting in the Nucleus: Metabolic Regulation of Gene Transcription

Boukouris

Zervopoulos

Michelakis

2016

Trends in Biochemical Sciences

243

206

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“…The generation of acetyl-CoA from both PFO and PDC is dependent on the glycolysis-derived product pyruvate. The nuclear presence of several metabolic enzymes has been observed as early as the 1960s, with many shown to interact with nuclear proteins and DNA and ''moonlight'' to the nucleus in conditions of cellular stress (Kim and Dang, 2005;Siebert and Humphrey, 1965;Yang et al, 2012;Yogev et al, 2010). For example, the M2 isoform of the glycolytic enzyme pyruvate kinase (PKM2) translocates to the nucleus and functions as a protein kinase, phosphorylating nuclear proteins, like threonine-11 of histone 3 (H3), and enhancing the acetylation of lysine 9 on H3 (H3K9) .…”

Section: Introductionmentioning

confidence: 99%

A Nuclear Pyruvate Dehydrogenase Complex Is Important for the Generation of Acetyl-CoA and Histone Acetylation

Sutendra

Kinnaird

Dromparis

et al. 2014

Cell

501

472

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DNA transcription, replication, and repair are regulated by histone acetylation, a process that requires the generation of acetyl-coenzyme A (CoA). Here, we show that all the subunits of the mitochondrial pyruvate dehydrogenase complex (PDC) are also present and functional in the nucleus of mammalian cells. We found that knockdown of nuclear PDC in isolated functional nuclei decreased the de novo synthesis of acetyl-CoA and acetylation of core histones. Nuclear PDC levels increased in a cell-cycle-dependent manner and in response to serum, epidermal growth factor, or mitochondrial stress; this was accompanied by a corresponding decrease in mitochondrial PDC levels, suggesting a translocation from the mitochondria to the nucleus. Inhibition of nuclear PDC decreased acetylation of specific lysine residues on histones important for G1-S phase progression and expression of S phase markers. Dynamic translocation of mitochondrial PDC to the nucleus provides a pathway for nuclear acetyl-CoA synthesis required for histone acetylation and epigenetic regulation.

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“…However, its intracellular distribution is not restricted to the cytoplasm. Rather, early reports on the presence of LDH in the nucleus date back to 1965 (Siebert and Humphrey 1965;Siebert et al 1966). More speciWcally, LDH-5 has been located to the nucleus, and evidence has been provided that it may function in the regulation of gene transcription or DNA replication.…”

Section: Discussionmentioning

confidence: 96%

Distribution of lactate dehydrogenase in healthy and degenerative canine stifle joint cartilage

Walter

Spreng

Schmöckel

et al. 2007

Histochem Cell Biol

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In dogs, degenerative joint diseases (DJD) have been shown to be associated with increased lactate dehydrogenase (LDH) activity in the synovial fluid. The goal of this study was to examine healthy and degenerative stifle joints in order to clarify the origin of LDH in synovial fluid. In order to assess the distribution of LDH, cartilage samples from healthy and degenerative knee joints were investigated by means of light and transmission electron microscopy in conjunction with immunolabeling and enzyme cytochemistry. Morphological analysis confirmed DJD. All techniques used corroborated the presence of LDH in chondrocytes and in the interterritorial matrix of healthy and degenerative stifle joints. Although enzymatic activity of LDH was clearly demonstrated in the territorial matrix by means of the tetrazolium-formazan reaction, immunolabeling for LDH was missing in this region. With respect to the distribution of LDH in the interterritorial matrix, a striking decrease from superficial to deeper layers was present in healthy dogs but was missing in affected joints. These results support the contention that LDH in synovial fluid of degenerative joints originates from cartilage. Therefore, we suggest that (1) LDH is transferred from chondrocytes to ECM in both healthy dogs and dogs with degenerative joint disease and that (2) in degenerative joints, LDH is released from chondrocytes and the ECM into synovial fluid through abrasion of cartilage as well as through enhanced diffusion as a result of increased water content and degradation of collagen.

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Enzymology of the Nucleus

Cited by 33 publications

References 139 publications

Metabolic Enzymes Moonlighting in the Nucleus: Metabolic Regulation of Gene Transcription

Metabolic Enzymes Moonlighting in the Nucleus: Metabolic Regulation of Gene Transcription

A Nuclear Pyruvate Dehydrogenase Complex Is Important for the Generation of Acetyl-CoA and Histone Acetylation

Distribution of lactate dehydrogenase in healthy and degenerative canine stifle joint cartilage

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