Succinate dehydrogenase and human diseases: new insights into a well-known enzyme

Rustin, Pierre; Münnich, Arnold; Rötig, Agnès

doi:10.1038/sj.ejhg.5200793

Cited by 220 publications

(168 citation statements)

References 20 publications

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“…The positive correlation between the increase in oxidative modification and the decrease in coupled and overall complex activity suggests that this modification affects either the substrate binding or the electron transfer ability of SDHA, or both. This is consistent with the observation that deficiency in and mutation of SDH subunits are known to cause severe diseases in humans and may thus support the argument that modifications in SDHA can lead to structural and functional changes similar to those caused by genetic mutations [34,35]. Thus, we show for the first time that the increase of in vivo oxidative modification of SDHA subunit directly correlates to an age-associated functional deficiency in CII.…”

Section: Discussionsupporting

confidence: 77%

Age-related increases in oxidatively damaged proteins of mouse kidney mitochondrial electron transport chain complexes

Choksi

Nuss

Boylston

et al. 2007

Free Radical Biology and Medicine

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Mitochondrial dysfunction generates reactive oxygen species (ROS) which damage essential macromolecules. Oxidative modification of proteins, DNA, and lipids has been implicated as a major causal factor in the age-associated decline in tissue function. Mitochondrial electron transport chain complexes I and III are the principle sites of ROS production, and oxidative modifications to the complex subunits inhibit their in vitro activity. Therefore, we hypothesize that mitochondrial complex subunits may be primary targets for oxidative damage by ROS which may impair normal complex activity by altering their structure/function leading to mitochondrial dysfunction associated with aging. This study of kidney mitochondria from young, middle-aged and old mice reveals that there are functional decreases in Complexes I, II, IV and V between aged compared to young kidney mitochondria and these functional declines directly correlate with increased oxidative modification to particular complex subunits. We postulate that the electron leakage from complexes causes specific damage to their subunits and increased ROS generation as oxidative damage accumulates, leading to further mitochondrial dysfunction, a cyclical process that underlies the progressive decline in physiologic function seen in aged mouse kidney. In conclusion, increasing mitochondrial dysfunction may play a key role in the age-associated decline in tissue function.

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Section: Discussionsupporting

confidence: 77%

Age-related increases in oxidatively damaged proteins of mouse kidney mitochondrial electron transport chain complexes

Choksi

Nuss

Boylston

et al. 2007

Free Radical Biology and Medicine

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“…Due to its unique redox properties, and in partnership with ubiquinone, SDH activity maintains a high reduction state of the ubiquinone pool which in turns improves the anti-oxidant capacity of mitochondria, and thus the resistance to oxidative stress [43]. Although we did not find any change in the activity of isolated complex II following treatment with CORM-3, further work should be undertaken to verify whether a direct effect of CO on this complex uncouples mitochondria in respiring cells.…”

Section: Discussioncontrasting

confidence: 43%

A carbon monoxide-releasing molecule (CORM-3) uncouples mitochondrial respiration and modulates the production of reactive oxygen species

Iacono

Boczkowski

Zini

et al. 2011

Free Radical Biology and Medicine

135

114

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“…Additionally, recent studies showed that complex II was an additional site of ROS generation (McLennan and Degli Esposti, 2000). Succinate dehyrogenase (SDH), which forms a part of complex II, catalyses the oxidation of succinate to fumarate in the Krebs cycle, and feeds electrons to the respiratory chain ubiquinone pool (Rustin et al, 2002). Previously, we showed that MeHg treatment increased O 2 -generation in the cerebellum mitochondria when succinate was used as a substrate (Mori et al, 2007).…”

Section: Resultsmentioning

confidence: 99%

Methylmercury inhibits electron transport chain activity and induces cytochrome c release in cerebellum mitochondria

et al. 2011

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-The involvement of oxidative stress has been suggested as a mechanism for toxicity caused by methylmercury (MeHg). One of the major critical sites for oxidative stress is the mitochondria. In this research, to clarify the target site in mitochondria affected by MeHg, the individual activities of the mitochondrial electron transport chain (ETC) (I IV) were examined in the liver, cerebrum and cerebellum of MeHg-intoxicated rats. In addition, to elucidate the mechanism underlying MeHg toxicity, cytochrome c release, caspase 3 activity and histological study were examined in the cerebrum and cerebellum. The cerebellum was found to be an exclusive tissue in which significant MeHg-induced alterations were observed. The complex II activity in the cerebellum mitochondria significantly decreased after MeHg exposure. Cytochrome c release from mitochondria increased only in the cerebellum by MeHg exposure. However, no significant alterations in caspase 3 activity or histological structure were found in brain tissues. These results suggest that MeHg acts on the constituents of complex II in the cerebellum, and induces mitochondrial dysfunction, leading to a release of cytochrome c from mitochondria. These events were considered to occur at the early stage of MeHg intoxication.

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Succinate dehydrogenase and human diseases: new insights into a well-known enzyme

Cited by 220 publications

References 20 publications

Age-related increases in oxidatively damaged proteins of mouse kidney mitochondrial electron transport chain complexes

Age-related increases in oxidatively damaged proteins of mouse kidney mitochondrial electron transport chain complexes

A carbon monoxide-releasing molecule (CORM-3) uncouples mitochondrial respiration and modulates the production of reactive oxygen species

Methylmercury inhibits electron transport chain activity and induces cytochrome c release in cerebellum mitochondria

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