Tuesday, 19 August 2014

Dynamics of nucleoid structure regulated by mitochondrial fission contributes to cristae reformation and release of cytochrome c


http://www.ncbi.nlm.nih.gov/pubmed/23821750


 In this paper they suggest that fission is needed to distribute mtDNA through the mitochondrial network, because if Drp1 is knocked out (and the mitochondria start to fuse) the nucleoids cluster together and large areas in the mitochondrial networks do not contain any mtDNA. This clustering starts 96 hours after Drp1 knockout (and later also 24 hours after Drp1 knockdown) and the total mtDNA content remains constant which means it really appears as though nucleoids diffuse through the mitochondrial network towards each other. If Drp1 is re-expressed, the effect is undone and the nucleoids distribute themselves again.

Knocking down Mff (mitochondrial fission factor), a protein that is also involved in mitochondrial fission, also causes clustering of nucleoids (nucleoid enlarging actually, that is what they really see). No enlarging is seen when OPA1 or MFN1,2 are knocked down and also not if both OPA1 and Drp1 are knocked down. Overexpression of MFN1 does lead to enlarged nucleoids.

When the enlarged nucleoids were observed at with higher resolution, it was clear that they consisted of several nucleoids clustered together.

They also observe that fission events tend to occur in the vicinity of nucleoids, this happened in 70% of the fission events seen (the number of which is 'several'). They then suggest that the distribution of Drp1 and Mff is responsible for nucleoid distribution.

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