Control of Succinate Dehydrogenase in Mitochondria

M. Gutman, Edna B. Kearney, Thomas P. Singer

Research output: Contribution to journalArticlepeer-review

Abstract

In intact, respiring mitochondria succinate dehydrogenase activity undergoes rapid and extensive changes in response to the metabolic state. Highest succinate dehydrogenase activity is observed in state 4, when coenzyme Q (CoQ) is largely in the reduced state. On transition to state 3 rapid deactivation of the enzyme occurs, in line with data in the literature showing oxidation of CoQ10 under these conditions. Lowest activity is observed in state 2 or in the presence of uncouplers, which cause almost complete oxidation of reduced CoQ10. These findings indicate that the activation of the dehydrogenase by reduced CoQ10 in membranes also operates in intact mitochondria and is one of the factors governing succinate dehydrogenase activity. The data also help explain reports in the literature of succinate accumulation in state 3 and in the presence of uncouplers and its metabolic removal in state 4. In addition to activation by reduced CoQ10 in mitochondria, the enzyme is also activated by succinate and by ATP or a compound in equilibrium with ATP. ATP-induced activation does not seem to involve oxalacetate removal and is not mediated by the energy conservation system, since it is not oligomycin sensitive. In submitochondrial particles and in complex II neither ATP nor GTP seems to activate the enzyme but ITP and IDP do. Activation of succinate dehydrogenase by succinate, substances leading to CoQ10 reduction, or ATP occuss more rapidly and with a lower activation energy in mitochondria than in submitochondrial particles or soluble preparations. These observations indicate that the dehydrogenase is under efficient multiple control in intact mitochondria.

Original languageEnglish
Pages (from-to)4763-4770
Number of pages8
JournalBiochemistry
Volume10
Issue number25
DOIs
StatePublished - 1 Dec 1971

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