Fig 9.

Model for multilayered regulation of the TCA cycle in B. subtilis. At the transcriptional level, the citZ gene is repressed by CcpA (not pictured), which is activated by high glucose levels. In addition, both citZ and citB are repressed by CcpC, which is active in the absence of citrate. When glucose is exhausted, CcpA is inactivated, and citZ is partially depressed, resulting in the production of a small amount of citrate. This citrate causes CcpC repression of citZ to be alleviated; however, CcpC also becomes a positive regulator of citB (11), resulting in an increase in Acn levels. The aconitase protein is present in two pools in the cell; the enzymatic form (Acn_Enz) and the RNA-binding form (Acn_RNA). The RNA-binding form of Acn interacts with the citZ mRNA at the posttranscriptional level and decreases its stability (dashed line), leading to decreases in citrate synthase levels and citrate production within the cell. In this manner, the cell utilizes a citrate-metabolizing enzyme, aconitase, to tightly control the levels of citrate within the cell by regulating both the enzyme that produces citrate, citrate synthase, and aconitase itself, making this model a form of autoregulatory loop.