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. Author manuscript; available in PMC: 2018 Jul 15.
Published in final edited form as: Biochem Pharmacol. 2017 Apr 9;136:86–98. doi: 10.1016/j.bcp.2017.03.025

Figure 12. Working hypothesis H2S stimulates LDHA activity and stimulates mitochondrial electron transport in colon cancer cells.

Figure 12

H2S increases the catalytic activity of LDHA (which is primary cytosolic, for instance, four LDHA tetramers constitute LDH5). This results in an increase in cytosolic lactate, followed by an increased flux of lactate into the mitochondria through the intracellular lactate shuttle. Lactate enters the mitochondrial intermembrane space; lactate and pyruvate also enter the mitochondrial matrix (the latter process is facilitated by the mitochondrial monocarboxylate transporter (mMCT). Lactate is oxidized to pyruvate via the mitochondrial LDH (which is primarily made up from LDHB; this response may also be stimulated by H2S). Pyruvate in the mitochondria is oxidized via the Krebs cycle to produce electron donors (NADH), which, in turn stimulates mitochondrial electron transport. In addition, the lactate-pyruvate conversion, catalyzed by mitochondrial LDH, utilizes NAD+ and produces NADH. This NADH, in turn, can be used by the mitochondrial electron chain to further support electron transport. IM, inner mitochondrial membrane; IMS, inner mitochondrial membrane space; OM, outer mitochondrial membrane.