Complex II ambiguities

high-resolution terminology - matching measurements at high-resolution

Complex II ambiguities

Description

The Succinate pathway is represented in the literature in some cases with a surprising confusion which warrants an analysis of Complex II ambiguities. The CII ambiguity has its roots in the narrative that reduced coenzymes (NADH and FADH₂) feed electrons from the Krebs cycle into the membrane-bound electron transfer system. In corresponding ambiguous graphical representations, CII in the canonical ('forward') Krebs cycle is shown to reduce FAD to FADH₂ (correct), yet CII in the membrane-bound electron transfer system is paradoxically represented as the site of oxidation of FADH₂ to FAD. For clarification: "The substrate of CII is succinate, which is oxidized forming fumarate while reducing flavin adenine dinucleotide FAD to FADH₂, with further electron transfer to the quinone pool. Whereas reduced NADH is a substrate of Complex I linked to dehydrogenases of the TCA cycle and mt-matrix upstream of CI, reduced FADH₂ is a product of Complex II with downstream electron flow from CII to Q" (quote from Gnaiger 2020).

Abbreviation: CII ambiguities

Reference: Gnaiger E (2020) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 5th ed. Bioenerg Commun 2020.2. https://doi.org/10.26124/bec:2020-0002

FADH₂ and S-pathway

• FADH₂ appears in several publications as the substrate of CII in the electron transfer system. This commonly found error requires correction. For clarification, see Gnaiger (2020) page 48.
• Links to FADH₂→CII misconceptions

• Arnold 2022 J Biol Chem
• Turton 2022 Int J Mol Sci
• Ahmad 2022 StatPearls Publishing
• Martinez-Reyes 2020 Nat Commun
• Yepez 2018 PLOS One
• Zhang 2018 Mil Med Res
• DeBerardinis 2016 Sci Adv
• Himms-Hagen 2001 Exp Biol Med (Maywood)
• Sanchez 2001 Br J Pharmacol
• Oxidative phosphorylation by OpenStax Biology (CC BY 3.0) got it wrong in figures and text, and the error is propagated further, with copies in

• Khan Academy
• LibreTexts Biology
• saylor.org Academy
• lumen Biology for Majors I
• Jack Westin MCAT Courses

• Conduct Science:"In Complex II, the enzyme succinate dehydrogenase in the inner mitochondrial membrane reduce FADH₂ to FAD⁺. Simultaneously, succinate, an intermediate in the Krebs cycle, is oxidized to fumarate." - Comments: FAD does not have a postive charge. FADH₂ is the reduced form, it is not reduced. And again: In CII, FAD is reduced to FADH₂.

CII and fatty acid oxidation

CII is not involved in fatty acid oxidation, which requires electron transferring flavoprotein CETF and CI. But there are confusing accounts of a rote of CII in fatty acid oxidation, which require correction:

• "Since mitochondrial Complex II also participates in the oxidation of fatty acids (6), .." (quote from [ Lemmi et al 1990]).

• Ref 6: Tzagoloff A (1982) Mitochondria. Plenum, New York.

• CHM333 LECTURES 37 & 38: 4/27 – 29/13 SPRING 2013 Professor Christine Hrycyna - Acyl-CoA dehydrogenase is listed under 'Electron transfer in Complex II'.

MitoPedia concepts: MiP concept 

MitoPedia topics: Enzyme, Substrate and metabolite 

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