Fig. 3.

Acetyl CoA synthesis in the mitochondrial matrix and the regulation of histone acetylations by redox components. In the cytoplasm, the breakdown of glucose produces pyruvate, which enters the tricarboxylic acid (TCA) cycle that occurs in the mitochondria. Then, pyruvate is converted to acetyl-CoA through mitochondrial pyruvate dehydrogenase (mPDH) by reducing NAD +. Combining with acetyl-CoA, oxaloacetate (OAA) formed in the TCA cycle produces citrate. After entering the cytoplasm, citrate is converted back to OAA and acetyl-CoA through ATP-citrate lyase (ACL). Synthesized acetyl-CoA enters the nucleus and provides the acetyl group to the histone acetyltransferase (HAT) for histone acetylation. After receiving the acetyl group, HAT introduces acetylation marks (Ac) over the lysine residues of the histone tail, thereby loosening the nucleosome structure (DNA and histones) and facilitating gene expression. Histone deacetylase (HDAC) removes histone acetyl groups from the histone tail, thus leading to chromatin compaction. ROS, NO, and NAD⁺ influence different HAT and HDAC enzymes [4]. The schematic representation was adapted from Saravana Kumar et al. [4].