Loss of SDH and blocking purine salvage inhibits cancer growth

The role of mitochondrial metabolism in modulating de novo purine synthesis pathway that plays a key role in nucleotide production is not well understood.

The researchers show that succinate dehydrogenase (SDH) maintains purine synthesis and SDH inhibition decreases cell proliferation. 

SDH inhibition elevates succinate, inducing  serine hydroxymethyltransferase 2 (SHMT2) 

 succinylation that suppresses mitochondrial one carbon flow and formate supply, thereby constraining purine assembly.

Cancer cells compensate via purine salvage, and dual inhibition of SDH and salvage yields significant antiproliferative effects and suppresses tumor growth.

https://www.cell.com/molecular-cell/fulltext/S1097-2765(25)00819-6

https://sciencemission.com/succinate-suppresses-de-novo-purine-synthesis