Mitochondrial DNA replication and OXPHOS gene transcription show varied responsiveness to Rieske protein knockdown in 143B cells
Date
2011Author
Levanets, Oksana
Reinecke, Fimmie
Louw, Roan
Pretorius, Pieter J.
Du Plessis, Lissinda H.
Van der Westhuizen, Francois H.
Metadata
Show full item recordAbstract
Genetic, biochemical and phenotypic diversity is a hallmark of OXPHOS deficiencies. Among the
responses frequently reported for these deficiencies is differential expression of several genes involved in
mitochondrial biogenesis. These responses are often associated with elevated oxygen radical production.
The genetic diversity of tissue and cell lines used in these investigations, however, complicates the
interpretation of observations. We investigated mtDNA copy number and selected transcriptional
responses after inducing stable Rieske protein knockdown in 143B cells. Despite the significant loss of
complex III activity, hydrogen peroxide levels remained comparable to controls. Furthermore, no
significant change in mtDNA copy number was observed. Mitochondrial L-strand- and D-loop transcript
levels remained unchanged, while the H-strand transcript for COXII was reduced. With the exception of
mitochondrial single-stranded binding protein (mtSSB), which was reduced, no transcriptional changes
of the mtDNA replication and transcription machinery were observed. Notably however, a selection of
nuclear-encoded OXPHOS gene transcripts was generally reduced (statistically insignificant), except for
NDUFS3 and COX4I1 transcripts, which were significantly reduced. From these results we conclude that
the induction of a low superoxide producing complex III deficiency in 143B cells has an insignificant
effect on mtDNA replication and function, but that expression of OXPHOS genes is generally down
regulated. This may indicate a lowering of mitochondrial biogenesis and a shift towards anaerobic energy
metabolism to improve cellular survival.
URI
http://hdl.handle.net/10394/17151https://www.sciencedirect.com/science/article/pii/S0300908411000095
https://doi.org/10.1016/j.biochi.2011.01.004