Long-chain acyl-CoA esters and acyl-CoA binding protein are present in the nucleus of rat liver cells

Abstract

A detailed analysis of the subcellular distribution of acyl-CoA esters in rat liver revealed that significant amounts of long-chain acyl-CoA esters are present in highly purified nuclei. No contamination of microsomal or mitochondrial marker enzymes was detectable in the nuclear fraction. C16:1 and C18:3-CoA esters were the most abundant species, and thus, the composition of acyl-CoA esters in the nuclear fraction deviates notably from the overall composition of acyl-CoA esters in the cell. After intravenous administration of the non-␤ -oxidizable [ 14 C]tetradecylthioacetic acid (TTA), the TTA-CoA ester could be recovered from the nuclear fraction. Acyl-CoA esters bind with high affinity to the ubiquitously expressed acyl-CoA binding protein (ACBP), and several lines of evidence suggest that ACBP functions as a pool former and transporter of acyl-CoA esters in the cytoplasm. By using immunohistochemistry, immunofluorescence microscopy, and immunoelectron microscopy we demonstrate that ACBP localizes to the nucleus as well as the cytoplasm of rat liver cell and rat hepatoma cells, suggesting that ACBP may also be involved in regulation of acyl-CoA-dependent processes in the nucleus. -Elholm, M.

PML isoform II plays a critical role in nuclear lipid droplet formation

“…5 C), which seemingly corresponded to its distribution in the ER and cytoplasmic LDs (Wilfling et al, 2013). Together with the nuclear presence of diacylglycerol and acyl-CoA (Elholm et al, 2000;Irvine, 2003), which are substrates of DGAT2, this result indicated that triglycerides could be synthesized in the nucleus. Furthermore, CCTα, the penultimate enzyme of the phosphatidylcholine synthetic Kennedy pathway that was reported to exist in cytoplasmic LDs (Krahmer et al, 2011), was also found around nuclear LDs (Figs.…”

Liver Fatty Acid-Binding Protein Colocalizes with Peroxisome Proliferator Activated Receptor α and Enhances Ligand Distribution to Nuclei of Living Cells

“…In summary, the results presented herein for the first time demonstrated that LCFA-CoA, as well as LCFA, is localized in the nucleoplasm and nuclear membrane of living cells. Thus, earlier suggestions regarding the presence of LCFA-CoAs (68) and unesterified LCFA in nuclei (isolated by subcellular fractionation) were not simply due to artifacts of nuclear isolation or hydrolytic cleavage of esterified lipids to release LCFAs (64,79,80). The 23-30% colocalization of L-FABP and PPARR as well as L-FABP-mediated enhancement of LCFA-CoA as well as LCFA targeting to nuclei, especially nucleoplasm, suggested that L-FABP may serve to shuttle LCFAs and LCFA-CoAs to and/or into the nucleus for donating the ligands to PPARR.…”

“…A priori, it is not possible to directly compare the distribution of BODIPY-C16-S-S-CoA with that of naturally occurring metabolizable LCFA-CoAs in living cells. To date, the only comparisons that can be made are with purified rat liver nuclei, whose LCFA-CoA content was 0.32 nmol/g wet weight (68). It was reported that the total LCFA-CoA concentration of rat liver cells ranges from 15 to 83 nmol/g wet weight (reviewed in refs 67 and 69).…”

Nuclear lipid droplets: A novel nuclear domain

“…nLD could thus be involved in nuclear-lipid homeostasis and serve as an endonuclear buffering system that can rapidly provide or incorporate lipids involved in these processes. The ultimate role of the nLD lipids could be the regulation of enzymes involved in nuclear-lipid metabolism, signaling events, and/or interactions with transcription factors such as the PPAR and the HNF 4 α that have FA as ligands [51]. Moreover, when these processes are shut down and the bound lipids (e.g., the FA, DG, phosphoinositides) are accordingly released from the specific active site and/or receptor, these lipidic regulatory ligands could become incorporated into nLD.…”