Abstract

SUCLA2-related mitochondria! DNA (mtDNA) depletion syndrome is a result of mutations in the beta 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. (C) 2011 Elsevier B.V. All rights reserved.

Keywords

mtDNA depletion; Succinyl-CoA synthase; SUCLA2; SUCLG2; NDPK; Mitochondrial respiratory chain

Published in

BBA - Molecular Basis of Disease
2011, Volume: 1812, number: 5, pages: 625-629
Publisher: ELSEVIER SCIENCE BV

SLU Authors

• Wang, Liya

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

UKÄ Subject classification

Biochemistry and Molecular Biology


Publication identifier

DOI: https://doi.org/10.1016/j.bbadis.2011.01.013

Permanent link to this page (URI)

https://res.slu.se/id/publ/46921