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Quality matters: how does mitochondrial network dynamics and quality control impact on mtDNA integrity?

Lookup NU author(s): Dr Axel Kowald


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Mammalian mtDNA encodes for 13 core proteins of oxidative phosphorylation. Mitochondrial DNA mutations and deletions cause severe myopathies and neuromuscular diseases. Thus, the integrity of mtDNA is pivotal for cell survival and health of the organism. We here discuss the possible impact of mitochondrial fusion and fission on mtDNA maintenance as well as positive and negative selection processes. Our focus is centred on the important question of how the quality of mtDNA nucleoids can be assured when selection and mitochondrial quality control works on functional and physiological phenotypes constituted by oxidative phosphorylation proteins. The organelle control theory suggests a link between phenotype and nucleoid genotype. This is discussed in the light of new results presented here showing that mitochondrial transcription factor A/nucleoids are restricted in their intramitochondrial mobility and probably have a limited sphere of influence. Together with recent published work on mitochondrial and mtDNA heteroplasmy dynamics, these data suggest first, that single mitochondria might well be internally heterogeneous and second, that nucleoid genotypes might be linked to local phenotypes (although the link might often be leaky). We discuss how random or site-specific mitochondrial fission can isolate dysfunctional parts and enable their elimination by mitophagy, stressing the importance of fission in the process of mtDNA quality control. The role of fusion is more multifaceted and less understood in this context, but the mixing and equilibration of matrix content might be one of its important functions.

Publication metadata

Author(s): Busch KB, Kowald A, Spelbrink JN

Publication type: Review

Publication status: Published

Journal: Philosophical Transactions of the Royal Society B-Biological Sciences

Year: 2014

Volume: 369

Issue: 1646

Pages: 1-12

Print publication date: 26/05/2014

ISSN (print): 0962-8436

ISSN (electronic): 1471-2970

Publisher: ROYAL SOC


DOI: 10.1098/rstb.2013.0442