An evolving view of complex II—noncanonical complexes, megacomplexes, respiration, signaling, and beyond
T.M. Iverson, Prashant K. Singh, Gary Cecchini
Abstract
Mitochondrial complex II is traditionally studied for its participation in two key respiratory processes: the electron transport chain and the Krebs cycle. There is now a rich body of literature explaining how complex II contributes to respiration. However, more recent research shows that not all of the pathologies associated with altered complex II activity clearly correlate with this respiratory role. Complex II activity has now been shown to be necessary for a range of biological processes peripherally related to respiration, including metabolic control, inflammation, and cell fate. Integration of findings from multiple types of studies suggests that complex II both participates in respiration and controls multiple succinate-dependent signal transduction pathways. Thus, the emerging view is that the true biological function of complex II is well beyond respiration. This review uses a semichronological approach to highlight major paradigm shifts that occurred over time. Special emphasis is given to the more recently identified functions of complex II and its subunits because these findings have infused new directions into an established field. Mitochondrial complex II is traditionally studied for its participation in two key respiratory processes: the electron transport chain and the Krebs cycle. There is now a rich body of literature explaining how complex II contributes to respiration. However, more recent research shows that not all of the pathologies associated with altered complex II activity clearly correlate with this respiratory role. Complex II activity has now been shown to be necessary for a range of biological processes peripherally related to respiration, including metabolic control, inflammation, and cell fate. Integration of findings from multiple types of studies suggests that complex II both participates in respiration and controls multiple succinate-dependent signal transduction pathways. Thus, the emerging view is that the true biological function of complex II is well beyond respiration. This review uses a semichronological approach to highlight major paradigm shifts that occurred over time. Special emphasis is given to the more recently identified functions of complex II and its subunits because these findings have infused new directions into an established field. Respiratory complex II (Fig. 1A, succinate dehydrogenase (SDH), canonically SDHA-SDHB-SDHC-SDHD, but with exceptions) is a heterotetrameric membrane-spanning enzyme first described in 1909 (1Thunberg T. Studien über die beeinflussung des gasaustausches des überlebenden froschmuskels durch verschiedene stoffe.Skand. Archiv. Pysiol. 1909; 22: 430-436Crossref Scopus (0) Google Scholar) and studied in its purified form for around a century. It has been long established that complex II is a key player in multiple respiratory processes (2Cecchini G. Function and structure of complex II of the respiratory chain.Annu. Rev. Biochem. 2003; 72: 77-109Crossref PubMed Scopus (365) Google Scholar, 3Cecchini G. Respiratory complex II: role in cellular physiology and disease.Biochim. Biophys. Acta. 2013; 1827: 541-542Crossref PubMed Scopus (19) Google Scholar). The first described role of complex II was as a bioenergetic complex catalyzing two distinct redox reactions in mitochondrial aerobic respiration (Fig. 1, B and C) (2Cecchini G. Function and structure of complex II of the respiratory chain.Annu. Rev. Biochem. 2003; 72: 77-109Crossref PubMed Scopus (365) Google Scholar, 3Cecchini G. Respiratory complex II: role in cellular physiology and disease.Biochim. Biophys. Acta. 2013; 1827: 541-542Crossref PubMed Scopus (19) Google Scholar, 4Iverson T.M. Catalytic mechanisms of complex II enzymes: a structural perspective.Biochim. Biophys. Acta. 2013; 1827: 648-657Crossref PubMed Scopus (48) Google Scholar). Here, complex II links oxidative phosphorylation (Fig. 1D) with the Krebs cycle (Fig. 2). Because of the energetics of aerobic respiration, complex II works in a defined catalytic direction under aerobic conditions where the enzyme oxidizes succinate to fumarate and concomitantly reduces the high potential ubiquinone to ubiquinol (Fig. 1C). Under anaerobic conditions with fumarate as the terminal electron acceptor, bacterial complex II homologs can proficiently perform the reverse reaction, i.e., the enzyme reduces fumarate to succinate and concomitantly oxidizes lower potential quinones such as menaquinone or rhodoquinone (5Van Hellemond J.J. Klockiewicz M. Gaasenbeek C.P. Roos M.H. Tielens A.G. Rhodoquinone and complex II of the electron transport chain in anaerobically functioning eukaryotes.J. Biol. Chem. 1995; 270: 31065-31070Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar, 6Van Hellemond J.J. Van Remoortere A. Tielens A.G. Schistosoma mansoni sporocysts contain rhodoquinone and produce succinate by fumarate reduction.Parasitology. 1997; 115: 177-182Crossref PubMed Scopus (0) Google Scholar, 7Tielens A.G. Van Hellemond J.J. The electron transport chain in anaerobically functioning eukaryotes.Biochim. Biophys. Acta. 1998; 1365: 71-78Crossref PubMed Scopus (122) Google Scholar, 8Hatchikian E.C. On the role of menaquinone-6 in the electron transport of hydrogen: fumarate reductase system in the strict anaerobe Desulfovibrio gigas.J. Gen. Microbiol. 1974; 81: 261-266PubMed Google Scholar). “Reverse” complex II activity has also been demonstrated in both mammalian mitochondria (9Kumar R. Landry A.P. Guha A. Vitvitsky V. Lee H.J. Seike K. et al.A redox cycle with complex II prioritizes sulfide quinone oxidoreductase-dependent H2S oxidation.J. Biol. Chem. 2022; 298101435Abstract Full Text Full Text PDF Scopus (13) Google Scholar, 10Spinelli J.B. Rosen P.C. Sprenger H.G. Puszynska A.M. Mann J.L. Roessler J.M. et al.Fumarate is a terminal electron acceptor in the mammalian electron transport chain.Science. 2021; 374: 1227-1237Crossref PubMed Scopus (54) Google Scholar) and bacteria (11Maklashina E. Berthold D.A. Cecchini G. Anaerobic expression of Escherichia coli succinate dehydrogenase: functional replacement of fumarate reductase in the respiratory chain during anaerobic growth.J. Bacteriol. 1998; 180: 5989-5996Crossref PubMed Google Scholar). This reverse activity occurs under conditions where the quinone pool is highly reduced and where the fumarate concentration is sufficient to affect the thermodynamic driving force of the reverse reaction (12Cecchini G. Complexities of complex II: sulfide metabolism in vivo.J. Biol. Chem. 2022; 298101661Abstract Full Text Full Text PDF Scopus (3) Google Scholar).Figure 2Complex II in the Krebs cycle. The Krebs cycle, also called the tricarboxylic acid cycle or the citric acid cycle, is an energy-harvesting process integral to aerobic respiration. The Krebs cycle uses a series of oxidation-reduction reactions on carboxylate-containing small molecules. The Krebs cycle contributes to oxidative phosphorylation in multiple ways. First, it produces reducing equivalents in the form of NADH, which is used by respiratory complex I. Second, the chemical intermediate succinate is used by complex II to provide another conduit for electrons to enter the respiratory chain. Coordinates used to develop this figure include human pyruvate dehydrogenase (PDB 6H55, (212Prajapati A. et and functional of the human complex a by and Full Text Full Text PDF PubMed Scopus Google (PDB G. R. and of two of and Biol. PubMed Scopus Google (PDB of with and PubMed Google human dehydrogenase (PDB T. and of human PubMed Scopus Google (PDB K. of with the of Biol. Chem. Full Text Full Text PDF PubMed Scopus Google succinate dehydrogenase (PDB A. et structure of mitochondrial respiratory complex Full Text Full Text PDF PubMed Scopus Google human (PDB and of human fumarate PubMed Scopus Google and dehydrogenase (PDB structure of mitochondrial dehydrogenase from and the structure for acid PubMed Google The dehydrogenase complex was from the E. coli (PDB structure of the of the Escherichia coli dehydrogenase Biol. PubMed Scopus Google the E. coli (PDB E. K. et structure of the of the from the dehydrogenase complex of Escherichia PubMed Scopus Google the (PDB T. structure of dehydrogenase from with and the E. coli (PDB structure of the from the of the dehydrogenase complex of Escherichia Biol. PubMed Scopus Google succinate to this respiratory complex II that metabolism and cell by a mitochondrial Chem. Biol. 2022; PubMed Scopus Google Scholar). There be multiple that complex II controls First, and complex II can form with during bacterial fumarate can a in the direction of the bacterial which in bacteria to and the direction of Complex II homologs that fumarate to the and for this with fumarate A. T. Cecchini G. M. of the direction of in bacteria by fumarate and fumarate Biol. PubMed Scopus (0) Google Scholar, G. A. Cecchini G. V. et associated with the complex of bacterial Biol. PubMed Scopus Google Scholar, E. K. et bacterial complex is more PubMed Scopus Google Scholar). complex II the of cellular of its The of succinate as a has over the by a mitochondrial Chem. Biol. 2022; PubMed Scopus Google Scholar, as Rev. Biol. PubMed Scopus Google Scholar). Complex II is the of succinate in a in complex II activity and of reverse activity (9Kumar R. Landry A.P. Guha A. Vitvitsky V. Lee H.J. Seike K. et al.A redox cycle with complex II prioritizes sulfide quinone oxidoreductase-dependent H2S oxidation.J. Biol. Chem. 2022; 298101435Abstract Full Text Full Text PDF Scopus (13) Google Scholar, 10Spinelli J.B. Rosen P.C. Sprenger H.G. Puszynska A.M. Mann J.L. Roessler J.M. et al.Fumarate is a terminal electron acceptor in the mammalian electron transport chain.Science. 2021; 374: 1227-1237Crossref PubMed Scopus (54) Google Scholar) succinate in two distinct a range of succinate is a of these et links cycle to by Full Text Full Text PDF PubMed Scopus Google Scholar, A. of Rev. PubMed Scopus Google Scholar). can also succinate which is a et acid cycle as for PubMed Scopus Google Scholar). complex II subunits affect by in A. et of respiratory complex II to metabolic PubMed Scopus Google Scholar, M. K. D.A. et function of in the respiratory chain and of the mitochondrial Full Text Full Text PDF PubMed Scopus Google Scholar, A. E. of complex II links to oxidative for PubMed Scopus Google Scholar, et of the mitochondrial complex from 2021; PubMed Scopus Google Scholar) (Fig. is a of a that is A. et of respiratory complex II to metabolic PubMed Scopus Google Scholar) because it has a lower complex Complex as a on and it is not this is a defined with or it is a of that be of complex (Fig. the of complex with altered A. et of respiratory complex II to metabolic PubMed Scopus Google Scholar, K. R. A. A. et of succinate metabolism bioenergetic in 2022; Full Text Full Text PDF Scopus Google Scholar). is not the in a membrane-spanning of the that is for with an called M. K. D.A. et function of in the respiratory chain and of the mitochondrial Full Text Full Text PDF PubMed Scopus Google Scholar, et of the mitochondrial complex from 2021; PubMed Scopus Google Scholar) (Fig. a multiple of both and that under respiratory conditions and have functional of and in succinate dehydrogenase Biol. Chem. Full Text Full Text PDF PubMed Scopus (0) Google Scholar). and the and and can both to but another of and in succinate dehydrogenase Biol. Chem. Full Text Full Text PDF PubMed Scopus (0) Google Scholar). the not and in as to can be in a complex with an called (Fig. the of this complex and its functional is M. G. V. et mitochondrial by succinate 2013; Full Text Full Text PDF PubMed Scopus Google Scholar, G. M. A. of succinate dehydrogenase by the mitochondrial has and on PubMed Scopus Google Scholar, K. et and mitochondrial and succinate dehydrogenase B to metabolism and Scholar, A. Lee G. et mitochondrial an and is in mitochondrial metabolic Biol. PubMed Scopus Google Scholar). is that or all of these have distinct cellular However, cellular succinate activity be by and of the complex II A. E. of complex II links to oxidative for PubMed Scopus Google Scholar, et metabolic of complex II and Scopus (0) Google and of these also be for complex II subunits that for complex II a these correlate with altered complex II was the first its biological role is semichronological of findings in the to highlight how the in the for complex II in the the studies on complex II used mitochondrial enzyme purified from with studies the enzyme on and of the dehydrogenase from Biol. Chem. Google Scholar, on I. and of the Biol. Chem. Full Text PDF PubMed Google Scholar, V. and of dehydrogenase from Biochem. Biophys. PubMed Scopus (0) Google Scholar). studies not the of complex II function but also used complex II as a to the of and the role of in Complex II has a of to its as a include of cellular and complex II has a by its and This to a that can be by redox to of these the more findings from this was the that the be to On the of Biophys. Acta. PubMed Google Scholar, V. on the of Biochem. Biophys. PubMed Scopus (0) Google Scholar). complex the to the the redox potential of the by M. K. A. Cecchini G. reductase of Escherichia coli that Biol. Chem. Full Text PDF PubMed Google Scholar). This in potential is for the succinate in the the complex II the of bacterial of the bacterial is that these more the of biological However, because of in in subunits of complex II on findings can be to the an bacterial complex II all have with mitochondrial complex II in the and subunits However, complex II homologs in the membrane-spanning subunits T.M. E. Cecchini G. for in complex Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). membrane-spanning subunits contain the and contain on bacterial complex II of R. V. G. K. et and of the of complex II a of electron and during ubiquinone Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. E. Cecchini G. of Escherichia coli with an and Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, E. Cecchini G. of the of complex II the of the Biol. Chem. Full Text Full Text PDF PubMed Scopus (0) Google Scholar) and how to function V. R. et of succinate dehydrogenase and 2003; PubMed Scopus Google of bacterial complex II on the succinate reaction in the The first studies on bacterial homologs in in a of the of complex II (Fig. 1, B and C) M. K. A. Cecchini G. reductase of Escherichia coli that Biol. Chem. Full Text PDF PubMed Google Scholar, dehydrogenase of in the Biochem. PubMed Google Scholar, J.J. K. succinate dehydrogenase of the and studies on the in and PubMed Google Scholar, to the in succinate PubMed Scopus Google Scholar, Cecchini G. A. I. et of in Escherichia coli fumarate of the and of the A. PubMed Scopus Google Scholar, Cecchini G. from to reductase of Escherichia Biol. Chem. Full Text PDF PubMed Google Scholar, I. Cecchini G. of of Escherichia coli fumarate reductase by Biol. Chem. Full Text PDF PubMed Google Scholar, A. Cecchini G. I. to in Escherichia coli fumarate reductase by PubMed Google Scholar, A. Cecchini G. I. et of to on the of the in Escherichia coli fumarate 1995; PubMed Google Scholar). of the of a in the Escherichia coli complex II and associated with a of a complex II PubMed Scopus Google Scholar, R. et of complex II of the mitochondrial respiratory chain in and PubMed Google Scholar). was that the of in the of succinate in the purified with the of and be for the of a metabolic enzyme and associated with a of a complex II PubMed Scopus Google Scholar, R. et of complex II of the mitochondrial respiratory chain in and PubMed Google Scholar). Here, the was of the of complex II activity and associated with a of a complex II PubMed Scopus Google Scholar, R. et of complex II of the mitochondrial respiratory chain in and PubMed Google Scholar). given that in is M. The mitochondrial is for and its in body cell with to Biol. PubMed Scopus Google of complex II catalytic function produces with the is in et links cycle to by Full Text Full Text PDF PubMed Scopus Google Scholar, A.M. of succinate dehydrogenase in mammalian PubMed Scopus Google Scholar, A. M. et dehydrogenase metabolic of mitochondria to Full Text Full Text PDF PubMed Scopus Google Scholar, K. G. et controls succinate-dependent of mitochondrial complex A. PubMed Scopus Google Scholar). of complex II activity or activity of has been associated with and more M. R. The of mitochondrial complex II PubMed Scopus Google Scholar). the bacterial complex II was the first with by (Fig. T.M. Cecchini G. of the Escherichia coli fumarate reductase respiratory PubMed Scopus Google Scholar, A. M. of fumarate reductase from PubMed Scopus Google Scholar). Here, the of both V. A.M. of a fumarate Biol. PubMed Scopus Google Scholar, and of a fumarate Biol. PubMed Scopus Google Scholar, Van J.J. and of the fumarate reductase of Biol. PubMed Scopus Google Scholar) and T.M. Cecchini G. of the Escherichia coli fumarate reductase respiratory PubMed Scopus Google Scholar, A. M. of fumarate reductase from PubMed Scopus Google Scholar) complex II homologs in bacterial anaerobic respiration the field. fumarate or these complex II fumarate to succinate A. on of a reductase from an Biol. Chem. Full Text PDF PubMed Google Scholar, and its role in the of by Bacteriol. PubMed Google Scholar, of fumarate reductase in anaerobic Microbiol. PubMed Scopus (0) Google Scholar, of metabolism in I. structural and functional in Escherichia coli associated with shifts the aerobic and anaerobic Biophys. Acta. PubMed Google Scholar). This reaction is the reverse of that during oxidative phosphorylation and the Krebs cycle. conditions for structure the of a approach on fumarate for a of the of fumarate (Fig. R. et of the in a bacterial fumarate a and PubMed Scopus Google Scholar, in fumarate Biophys. Acta. PubMed Scopus Google Scholar, et to as an acid in a fumarate PubMed Scopus Google Scholar, et of in the fumarate reductase from PubMed Scopus (0) Google Scholar, E. T.M. V. et al.Fumarate reductase and succinate activity of Escherichia coli complex II homologs by of the Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, J.M. et al.A in the fumarate reductase from Biol. Chem. Full Text Full Text PDF PubMed Scopus (0) Google Scholar, T.M. E. Cecchini G. T.M. on the controls in Escherichia coli respiratory complex Biol. Chem. Full Text Full Text PDF PubMed Scopus (0) Google Scholar). of and mitochondrial complex II from in the G. et acid is a of mitochondrial respiration by complex a with a catalytic in the of the Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, A. et structure of mitochondrial respiratory complex Full Text Full Text PDF PubMed Scopus Google Scholar). for the of the membrane-spanning of the mitochondrial studies with to how quinone is in the mitochondria G. et acid is a of mitochondrial respiration by complex a with a catalytic in the of the Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, A. et structure of mitochondrial respiratory complex Full Text Full Text PDF PubMed Scopus Google Scholar, of the ubiquinone of respiratory Complex II and its Biophys. 2021; Scopus Google Scholar). in have also been to of the complex II for structure of complex II et structure of succinate dehydrogenase with a PubMed Scopus Google Scholar, M. and to of 2021; PubMed Scopus Google Scholar, et of the succinate dehydrogenase with a A. 2021; Scopus Google Scholar, A. R. T. V. et of mitochondrial by PubMed Scopus (0) Google Scholar). this of and of complex II homologs have now been from a range of and There complex II in the as in the of and quinone V. R. et of succinate dehydrogenase and 2003; PubMed Scopus Google Scholar, T.M. Cecchini G. of the Escherichia coli fumarate reductase respiratory PubMed Scopus Google Scholar, A. M. of fumarate reductase from PubMed Scopus Google Scholar, G. et acid is a of mitochondrial respiration by complex a with a catalytic in the of the Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, A. et structure of mitochondrial respiratory complex Full Text Full Text PDF PubMed Scopus Google Scholar, et structure of succinate dehydrogenase with a PubMed Scopus Google Scholar, M. and to of 2021; PubMed Scopus Google Scholar, A. R. T. V. et of mitochondrial by PubMed Scopus (0) Google Scholar, A. K. T. et structure of mitochondrial reductase from the Biochem. PubMed Scopus (0) Google Scholar, A. et structure of A. 2021; Scopus Google Scholar). distinct complex II of the of complex II (Fig. V. structure of complex II: an perspective.Biochim. Biophys. PubMed Scopus (0) Google Scholar). The structural the subunits for the of that the quinone the of complex II to the Krebs cycle with respiration is for and of including and T. et oxidative metabolism to 22: Full Text Full Text PDF PubMed Scopus (87) Google Scholar, Lee et al.A the role of fumarate in the of Escherichia PubMed Scopus (0) Google Scholar, T. M. et dehydrogenase is the of respiration in Scopus Google Scholar, I. K. M. T. et of succinate dehydrogenase in and its role in the of the potential under PubMed Scopus Google Scholar, R. M. M. of of succinate dehydrogenase in Bacteriol. PubMed Scopus Google Scholar, R. T. succinate reductase is and in PubMed Scopus (0) Google Scholar, of succinate metabolism in to in A. 2013; PubMed Scopus Google Scholar). Complex II have long been used as complex II the of The research in and of potential succinate dehydrogenase Chem. 2021; PubMed Scopus Google Scholar). complex II to human this the of complex from A. K. T. et structure of mitochondrial reductase from the Biochem. PubMed Scopus (0) Google Scholar) and et structure of succinate dehydrogenase with a PubMed Scopus Google Scholar, et of the succinate dehydrogenase with a A. 2021; Scopus Google have the for of for these to T. T. M. et into the of for fumarate respiration of PubMed Scopus Google Scholar, K. A. et for the of the of to produce new Biophys. Biol. PubMed Scopus Google Scholar). There also for homologs of complex these not the that is by the complex II complex II homologs include fumarate from that contain a V. A.M. of a fumarate Biol. PubMed Scopus Google Scholar, and of a fumarate Biol. PubMed Scopus Google Scholar, Van J.J. and of the fumarate reductase of Biol. PubMed Scopus Google Scholar) (Fig. fumarate reductase from that not contain a Lee et of an under by fumarate PubMed Scopus Google Scholar) (Fig. and from E. coli A. G. A. A. of for the succinate reductase Full Text Full Text PDF PubMed Scopus Google Scholar, A. G. A. of into and PubMed Scopus (0) Google Scholar). The to now to be for respiratory A. R. T. V. et of mitochondrial by PubMed Scopus (0) Google Scholar, K. The of respiratory PubMed Scopus Google Scholar, M. R. K. et of the mammalian PubMed Google Scholar, I. and of the mammalian mitochondrial 2021; PubMed Scopus (0) Google Scholar, T. H.J. M. et of and the 2021; PubMed Scopus Google Scholar, A. et electron transport by PubMed Scopus Google Scholar, A. R. et electron subunits of a respiratory Scopus Google Scholar, A.M. A. et of in a with Biol. PubMed Scopus (0) Google Scholar, A.M. A. in of of mitochondrial A. PubMed Scopus Google Scholar, et of a functional complex respiratory from Biol. PubMed Scopus (0) Google Scholar, A. et for and in a respiratory 2022; PubMed Scopus Google Scholar, Lee M. et al.A pool by of a respiratory 2022; PubMed Scopus Google Scholar, M. R. M. of mammalian respiratory Full Text Full Text PDF PubMed Scopus Google Scholar, M. structure of the respiratory from PubMed Scopus (0) Google Scholar, R. M. M. of human mitochondrial respiratory Full Text Full Text PDF PubMed Scopus Google Scholar, M. A. of respiratory chain the of 2022; PubMed Scopus (0) Google Scholar). called these contain more respiratory The for of respiration, or the and of respiration by to respiratory Complex II is from all K. The of respiratory PubMed Scopus Google Scholar, M. R. K. et of the mammalian PubMed Google Scholar, I. and of the mammalian mitochondrial 2021; PubMed Scopus (0) Google Scholar, T. H.J. M. et of and the 2021; PubMed Scopus Google Scholar, A. et electron transport by PubMed Scopus Google Scholar, A. R. et electron subunits of a respiratory Scopus Google Scholar, A.M. A. et of in a with Biol. PubMed Scopus (0) Google Scholar, A.M. A. in of of mitochondrial A. PubMed Scopus Google Scholar, et of a functional complex respiratory from Biol. PubMed Scopus (0) Google Scholar, A. et for and in a respiratory 2022; PubMed Scopus Google Scholar, Lee M. et al.A pool by of a respiratory 2022; PubMed Scopus Google Scholar, M. R. M. of mammalian respiratory Full Text Full Text PDF PubMed Scopus Google Scholar, M. structure of the respiratory from PubMed Scopus (0) Google Scholar, R. M. M. of human mitochondrial respiratory Full Text Full Text PDF PubMed Scopus Google Scholar, M. A. of respiratory chain the of 2022; PubMed Scopus (0) Google Scholar) but A. R. T. V. et of mitochondrial by PubMed Scopus (0) Google Scholar) of these it is complex II in the to its (Fig. and A. R. T. V. et of mitochondrial by PubMed Scopus (0) Google Scholar). This to a that complex II into the the that the this also suggests that not contain complex The lower of complex II for from how it with the Complex II has the of of the the of the complex II on the of the is from with the by a defined This suggests that complex II is associated with and that of the complex II is these the function of complex II is in the chemical reactions that to respiration and it more associated with the it it is not associated with the is that complex II participates in for such a role is in bacterial Here, the anaerobic complex II fumarate to the complex A. T. Cecchini G. M. of the direction of in bacteria by fumarate and fumarate Biol. PubMed Scopus (0) Google Scholar, G. A. Cecchini G. V. et associated with the complex of bacterial Biol. PubMed Scopus Google Scholar, E. K. et bacterial complex is more PubMed Scopus Google Scholar). This the of the bacterial and is for in to fumarate A. T. Cecchini G. M. of the direction of in bacteria by fumarate and fumarate Biol. PubMed Scopus (0) Google Scholar, G. A. Cecchini G. V. et associated with the complex of bacterial Biol. PubMed Scopus Google Scholar, E. K. et bacterial complex is more PubMed Scopus Google Scholar). the of a Krebs Krebs cycle structural of by and Chem. PubMed Google Scholar, Krebs cycle concentration of PubMed Google which contain complex Krebs the of the Krebs cycle by defined for small from enzyme to the Krebs cycle structural of by and Chem. PubMed Google Scholar, Krebs cycle concentration of PubMed Google Scholar). the in the an of functions for complex II to be with a in the is that complex II is not associated with a defined of This also in the in in an in the of the complex II which have been into The an for succinate dehydrogenase in and mitochondrial complex II PubMed Scopus Google Scholar). small of associated with the associated with types of This is with chemical of the by the V. A. et of the mechanisms of acid as a in a and its to and PubMed Scopus (0) Google Scholar). of and has been used in to V. A. et of the mechanisms of acid as a in a and its to and PubMed Scopus (0) Google Scholar). of mitochondrial in with a that have a for oxidative chemical of complex is used as a for as it in the of M. of beyond mitochondrial complex PubMed Scopus Google Scholar). it is not the reduced function of electron of this that of complex II mitochondrial (Fig. The of complex II in the and subunits The an for succinate dehydrogenase in and mitochondrial complex II PubMed Scopus Google Scholar). with complex II in the or correlate with types of in T.M. E. Cecchini G. for in complex Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, The an for succinate dehydrogenase in