scholarly journals The mitochondrial single-stranded DNA binding protein is essential for initiation of mtDNA replication

2021 ◽  
Vol 7 (27) ◽  
pp. eabf8631
Author(s):  
Min Jiang ◽  
Xie Xie ◽  
Xuefeng Zhu ◽  
Shan Jiang ◽  
Dusanka Milenkovic ◽  
...  

We report a role for the mitochondrial single-stranded DNA binding protein (mtSSB) in regulating mitochondrial DNA (mtDNA) replication initiation in mammalian mitochondria. Transcription from the light-strand promoter (LSP) is required both for gene expression and for generating the RNA primers needed for initiation of mtDNA synthesis. In the absence of mtSSB, transcription from LSP is strongly up-regulated, but no replication primers are formed. Using deep sequencing in a mouse knockout model and biochemical reconstitution experiments with pure proteins, we find that mtSSB is necessary to restrict transcription initiation to optimize RNA primer formation at both origins of mtDNA replication. Last, we show that human pathological versions of mtSSB causing severe mitochondrial disease cannot efficiently support primer formation and initiation of mtDNA replication.

2001 ◽  
Vol 12 (4) ◽  
pp. 821-830 ◽  
Author(s):  
Dieter Maier ◽  
Carol L. Farr ◽  
Burkhard Poeck ◽  
Anuradha Alahari ◽  
Marion Vogel ◽  
...  

The discovery that several inherited human diseases are caused by mtDNA depletion has led to an increased interest in the replication and maintenance of mtDNA. We have isolated a new mutant in thelopo (low power) gene fromDrosophila melanogaster affecting the mitochondrial single-stranded DNA-binding protein (mtSSB), which is one of the key components in mtDNA replication and maintenance.lopo 1 mutants die late in the third instar before completion of metamorphosis because of a failure in cell proliferation. Molecular, histochemical, and physiological experiments show a drastic decrease in mtDNA content that is coupled with the loss of respiration in these mutants. However, the number and morphology of mitochondria are not greatly affected. Immunocytochemical analysis shows that mtSSB is expressed in all tissues but is highly enriched in proliferating tissues and in the developing oocyte.lopo 1 is the first mtSSB mutant in higher eukaryotes, and its analysis demonstrates the essential function of this gene in development, providing an excellent model to study mitochondrial biogenesis in animals.


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