Table 1.

Additional sites of superoxide production in mitochondria by enzyme, substrate, iso-potential group, source and topology. Commentary is provided as appropriate.

Enzyme	Substrate	Group	Source/Topology	Comments
Alpha keto glutarate dehydrogenase	Alpha keto glutarate.	NAD+/NADH	FAD of E3 dihydrolipoamide dehydrogenase. Matrix.	ROS production is inhibited by high ATP and aspartate [69] and regulated by reversible thiol oxidation [105]. Favored by high NAD+/NADH ratio. May also produce H2O2. Requires substrate. Ca2+ sensitive.
Pyruvate dehydrogenase	Pyruvate.	NAD+/NADH	FAD of E3 dihydrolipoamide dehydrogenase. Matrix.	Regulated by reversible thiol oxidation [105] and phosphorylation. ROS production is favored by high NAD+/ NADH ratio. May also produce H2O2. Requires substrate.
Branched-chain 2-oxoacid dehydrogenase complex	Branched chain 2-oxoacids (e.g., 3-methyl-2-oxopentanoate).	NAD+/NADH	FAD of E3 dihydrolipoamide dehydrogenase. Matrix	Favored by high NAD+/NADH ratio. Requires substrate.
Aminoadipate dehydrogenase complex	2-oxoadipate.	NAD+/NADH	FAD of E3 dihydrolipoamide dehydrogenase. Matrix	ROS production is favored by high NADH/NAD+ ratio. Requires substrate.
sn-glycerol-3-phosphate dehydrogenase	Glycerol 3-phosphate	UQ/UQH2	UQ binding site but may also involve a flavin. Intermembrane space and matrix.	Ca2+ sensitive—can enhance ROS production at low substrate levels [106]. Requires substrate. Much emanates from complex II.
Dihydroorotate dehydrogenase	Dihydroorotate	UQ/UQH2	UQ binding site. Matrix.	Relatively low superoxide producing capacity but can drive other sites to high rates by reducing the Q pool [107].
Electron transferring-flavoprotein: ubiquinone oxidoreductase	Electron transferring flavoprotein (involved in lipid + amino acid metabolism).	UQ/UQH2	May emanate from the flavin but origin is unclear [69].	ROS production is quite low even when other sites are inhibited [108], suggesting main contribution under native conditions is to reduce the Q pool.