The interplay between SUCLA2, SUCLG2, and mitochondrial DNA depletion

Biochim Biophys Acta. 2011 May;1812(5):625-9. doi: 10.1016/j.bbadis.2011.01.013. Epub 2011 Feb 2.


SUCLA2-related mitochondrial DNA (mtDNA) depletion syndrome is a result of mutations in the β subunit of the ADP-dependent isoform of the Krebs cycle succinyl-CoA synthase (SCS). The mechanism of tissue specificity and mtDNA depletion is elusive but complementation by the GDP-dependent isoform encoded by SUCLG2, and the association with mitochondrial nucleoside diphosphate kinase (NDPK), is a plausible link. We have investigated this relationship by studying SUCLA2 deficient fibroblasts derived from patients and detected normal mtDNA content and normal NDPK activity. However, knockdown of SUCLG2 by shRNA in both patient and control fibroblasts resulted in a significant decrease in mtDNA amount, decreased NDPK and cytochrome c oxidase activities, and a marked growth impairment. This suggests that, SUCLG2, to a higher degree than SUCLA2, is crucial for mtDNA maintenance and that mitochondrial NDPK is involved. Although results pertain to a cell culture system, the findings might explain the pathomechanism and tissue specificity in mtDNA depletion caused by defective SUCLA2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Coenzyme A / metabolism
  • Cells, Cultured
  • DNA, Mitochondrial / metabolism*
  • Electron Transport Complex IV / metabolism
  • Fibroblasts / metabolism
  • Homozygote
  • Humans
  • Immunoenzyme Techniques
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Mutation / genetics
  • Nucleoside-Diphosphate Kinase / metabolism
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Succinate-CoA Ligases / antagonists & inhibitors
  • Succinate-CoA Ligases / genetics
  • Succinate-CoA Ligases / metabolism*


  • Acyl Coenzyme A
  • DNA, Mitochondrial
  • RNA, Messenger
  • RNA, Small Interfering
  • succinyl-coenzyme A
  • Electron Transport Complex IV
  • Nucleoside-Diphosphate Kinase
  • Succinate-CoA Ligases
  • SUCLA2 protein, human