Abstract:
:Mutations in succinate dehydrogenase (SDH) are associated with tumor development and neurodegenerative diseases. Only in tumors, loss of SDH activity is accompanied with the loss of complex I activity. Yet, it remains unknown whether the metabolic phenotype of SDH mutant tumors is driven by loss of complex I function, and whether this contributes to the peculiarity of tumor development versus neurodegeneration. We addressed this question by decoupling loss of SDH and complex I activity in cancer cells and neurons. We found that sole loss of SDH activity was not sufficient to recapitulate the metabolic phenotype of SDH mutant tumors, because it failed to decrease mitochondrial respiration and to activate reductive glutamine metabolism. These metabolic phenotypes were only induced upon the additional loss of complex I activity. Thus, we show that complex I function defines the metabolic differences between SDH mutation associated tumors and neurodegenerative diseases, which could open novel therapeutic options against both diseases.
journal_name
Metab Engjournal_title
Metabolic engineeringauthors
Lorendeau D,Rinaldi G,Boon R,Spincemaille P,Metzger K,Jäger C,Christen S,Dong X,Kuenen S,Voordeckers K,Verstreken P,Cassiman D,Vermeersch P,Verfaillie C,Hiller K,Fendt SMdoi
10.1016/j.ymben.2016.11.005subject
Has Abstractpub_date
2017-09-01 00:00:00pages
187-197issue
Pt Beissn
1096-7176issn
1096-7184pii
S1096-7176(16)30217-8journal_volume
43pub_type
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