ATP Citrate Lyase: A New Player Linking Skeletal Muscle Metabolism and Epigenetics

Abstract

Intermediates generated in several metabolic processes are used to regulate transcription through covalent histone and DNA modifications. In Cell Reports, Das et al. show that acetyl-coenzyme A (acetyl-CoA) generated by ATP citrate lyase (ACL) is utilized to acetylate histone H3 at MyoD regulatory regions, resulting in increased MyoD expression and improved muscle regeneration after injury.

Genetic deletion of skeletal muscle iPLA2γ results in mitochondrial dysfunction, muscle atrophy and alterations in whole-body energy metabolism

“…Although expression levels of the myogenic regulatory factor MyoD were essentially unchanged in the SKMiPLA 2 γKO in comparison to WT controls, markedly increased expression of Myogenin due to iPLA 2 γ loss of function in skeletal muscle is indicative of more active regenerative myogenesis in SKMiPLA 2 γKO vs. WT mice ( Figure 2 I). Furthermore, the expression level of ATP citrate lyase (ACL), a key enzyme regulating muscle cell growth/differentiation, muscle type transition, and mitochondrial function, 18 , 19 and its active (phosphorylated at Ser455) form were moderately upregulated in SKMiPLA 2 γKO mouse TA muscle likely facilitating skeletal muscle regeneration and the observed increase in fast skeletal myosin expression ( Figure 2 I).…”

Epigenetics in osteoarthritis: Novel spotlight

“…The acetyl‐CoA produced by this enzyme is used as a substrate by the histone acetyltransferases (HAT) to modulate acetylation of histones. Additionally, acetyl‐CoA can be used for the acetylation of transcription factors, such as p65 NF‐κB (Das et al, ; H. Li & Sartorelli, ). The activity of ACLY and consequently H3K9 and H3K27 acetylation was shown to be increased in human knee OA chondrocytes.…”

“…The acetyl-CoA produced by this enzyme is used as a substrate by the histone acetyltransferases (HAT) to modulate acetylation of histones. Additionally, acetyl-CoA can be used for the acetylation of transcription factors, such as p65 NF-κB (Das et al, 2017;H. Li & Sartorelli, 2018).…”

Biological Behavior and Lipid Metabolism of Colon Cancer Cells are Regulated by a Combination of Sterol Regulatory Element-Binding Protein 1 and ATP Citrate Lyase

“… 14 Inhibition of ACLY can delay the occurrence of tumors. 15 , 16 To date, a large number of studies have been carried out to confirm the importance of ACLY in alcoholic fatty liver, coronary atherosclerosis, tumors, and other diseases. For example, a previous study showed that the consumption of fish oil reduced blood lipids and restrained the activity of ACLY by downregulating SREBP1 in humans.…”