The interplay between SUCLA2, SUCLG2, and mitochondrial DNA depletion.

Chaya Miller, Liya Wang, Elsebet Ostergaard, Phyllis Dan, Ann Saada

Biochimica et biophysica acta 2011 May

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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. Copyright © 2011 Elsevier B.V. All rights reserved.

Citation

Chaya Miller, Liya Wang, Elsebet Ostergaard, Phyllis Dan, Ann Saada. The interplay between SUCLA2, SUCLG2, and mitochondrial DNA depletion. Biochimica et biophysica acta. 2011 May;1812(5):625-9