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@article{Hoitzing:2019:10.1371/journal.pcbi.1007023,
author = {Hoitzing, H and Gammage, PA and Haute, LV and Minczuk, M and Johnston, IG and Jones, NS},
doi = {10.1371/journal.pcbi.1007023},
journal = {PLoS Computational Biology},
title = {Energetic costs of cellular and therapeutic control of stochastic mitochondrial DNA populations},
url = {http://dx.doi.org/10.1371/journal.pcbi.1007023},
volume = {15},
year = {2019}
}
TY - JOUR
AB - The dynamics of the cellular proportion of mutant mtDNA molecules is crucial for mitochondrial diseases. Cellular populations of mitochondria are under homeostatic control, but the details of the control mechanisms involved remain elusive. Here, we use stochastic modelling to derive general results for the impact of cellular control on mtDNA populations, the cost to the cell of different mtDNA states, and the optimisation of therapeutic control of mtDNA populations. This formalism yields a wealth of biological results, including that an increasing mtDNA variance can increase the energetic cost of maintaining a tissue, that intermediate levels of heteroplasmy can be more detrimental than homoplasmy even for a dysfunctional mutant, that heteroplasmy distribution (not mean alone) is crucial for the success of gene therapies, and that long-term rather than short intense gene therapies are more likely to beneficially impact mtDNA populations.
AU - Hoitzing,H
AU - Gammage,PA
AU - Haute,LV
AU - Minczuk,M
AU - Johnston,IG
AU - Jones,NS
DO - 10.1371/journal.pcbi.1007023
PY - 2019///
SN - 1553-734X
TI - Energetic costs of cellular and therapeutic control of stochastic mitochondrial DNA populations
T2 - PLoS Computational Biology
UR - http://dx.doi.org/10.1371/journal.pcbi.1007023
UR - https://www.ncbi.nlm.nih.gov/pubmed/31242175
UR - http://hdl.handle.net/10044/1/71289
VL - 15
ER -