Nuclear Biophysics & Mechanics

Nuclear Metabolism: Acetyl-CoA and Local ATP Evidence

HTML scientific appraisal: 3 October 2026 | Source document separately unvalidated

Selected primary evidence connecting metabolite production with chromatin

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This HTML presents a selective primary-evidence overview. Every retained scientific paragraph and reference was appraised at the access depth listed below. Detailed Methods, raw data, exhaustive literature coverage and the associated source document remain outside the checked scope.

Cellular carbon supply and histone acetylation

Wellen and colleagues linked ATP-citrate lyase, which produces acetyl-CoA from citrate, with histone acetylation in mammalian cells. Growth-factor and differentiation-associated increases, and responses to glucose availability, depended on this enzyme in their experimental models. [wellen2009]

The findings connect cellular metabolism with a chromatin modification. Cellular enzyme dependence does not by itself establish a separate, autonomous nuclear metabolic circuit or control of every histone mark. [wellen2009]

Evidence for acetyl-CoA generation in nuclei

Sutendra and colleagues reported functional pyruvate-dehydrogenase-complex subunits in mammalian nuclei. In isolated functional nuclei, reduced nuclear complex activity was associated with less newly synthesized acetyl-CoA and core-histone acetylation. [sutendra2014]

Reciprocal changes in nuclear and mitochondrial complex abundance led the authors to suggest redistribution between compartments. Those abundance observations are distinct from directly tracking a protein's movement, and fraction-purity controls were not inspected at Abstract depth. [sutendra2014]

A stimulus-associated nuclear ATP route

Wright and colleagues reported ADP-ribose-derived nuclear ATP generation involving NUDIX5 in progestin-responsive breast cancer cells. Their Abstract links this route with hormone-associated chromatin remodeling, transcription and proliferation. [wright2016]

This is evidence for a particular stimulus and cell context. It does not establish the dominant ATP source in every nucleus, a universal metabolic rate or a treatment recommendation. [wright2016]

Interpreting local metabolic evidence

The studies distinguish cellular substrate supply, nuclear acetyl-CoA production and stimulus-associated ATP generation. They support specific links with chromatin while leaving whole-cell exchange, compartment purity and model dependence central to interpretation. [wellen2009] [sutendra2014] [wright2016]

Primary Abstracts and bibliographic identities were inspected. Detailed localization controls, all flux measurements, raw data and quantitative tissue-wide generalizations were not independently appraised. [wellen2009] [sutendra2014] [wright2016]

Primary references and access depth

  1. Wellen KE et al. (2009). ATP-citrate lyase links cellular metabolism to histone acetylation. Science (New York, N.Y.) 324:1076-80. PMID 19461003. DOI 10.1126/science.1164097. Access: Abstract and citation record.
  2. Sutendra G et al. (2014). A nuclear pyruvate dehydrogenase complex is important for the generation of acetyl-CoA and histone acetylation. Cell 158:84-97. PMID 24995980. DOI 10.1016/j.cell.2014.04.046. Access: Abstract and citation record.
  3. Wright RH et al. (2016). ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is required for chromatin remodeling. Science (New York, N.Y.) 352:1221-5. PMID 27257257. DOI 10.1126/science.aad9335. Access: Abstract and citation record.

Nuclear position and mitochondrial proximity provide distinct recent examples

A Willnow and Teleman (2024) linked nuclear position near the epithelial surface with increased acetyl-CoA synthase and histone acetylation. Fatty-acid oxidation contributed to that tissue pattern. These spatial and metabolic perturbations provide a defined tissue context; they do not establish an autonomous metabolic circuit in every nucleus. Willnow and Teleman (2024).

The Ghose et al. (2025) reported mitochondrial repositioning toward the nuclear periphery and a nuclear ATP rise sensitive to mitochondrial ATP production and actin organization. This offers a mitochondria-associated route alongside the stimulus-specific NUDIX5 route above. It does not establish that one source supplies most ATP in every nuclear compartment. Ghose et al. (2025).

Additional primary references

  1. Willnow and Teleman (2024). Nuclear position and local acetyl-CoA production regulate chromatin state. Nature. DOI: 10.1038/s41586-024-07471-4. Primary study. Access in this reassessment: primary abstract and bibliographic record.
  2. Ghose et al. (2025). Mitochondria-derived nuclear ATP surge protects against confinement-induced proliferation defects. Nature Communications. DOI: 10.1038/s41467-025-61787-x. Primary study. Access in this reassessment: primary abstract and bibliographic record.

Reassessed 12 October 2026. Recent-source access is stated above; complete supplementary material and raw data were not reanalysed. The archived Word draft remains a separate, unreconciled document.