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. 2015 Sep 30;8(4):675–695. doi: 10.3390/ph8040675

Figure 2.

Figure 2

Mitochondrial dysfunction caused by inhibition of pyruvate transfer to mitochondria. The activity of the PDH complex is blocked by PDK enzymes. PDK1 can phosphorylate all three sites—S1, S2, and S3 (Ser-264, Ser-271, and Ser-203, respectively) whereas PDK2, PDK3, and PDK4 each phosphorylate only the sites S1 and S2. After phosphorylation, mitochondrial energy production depends only on fatty acids. Both isoenzymes of pyruvate dehydrogenase phosphatase (PDP1 and PDP2) can reactivate phosphorylated PDH enzymes [27]. Mitochondrial dysfunction transforms chemical changes into biophysical pathological processes along the transformation pathway to cancer.