Publications

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Citation

BibTex format

@article{Aryaman:2019:10.1534/genetics.119.302423,
author = {Aryaman, J and Bowles, C and Jones, NS and Johnston, IG},
doi = {10.1534/genetics.119.302423},
journal = {Genetics},
pages = {1429--1443},
title = {Mitochondrial network state scales mtDNA genetic dynamics},
url = {http://dx.doi.org/10.1534/genetics.119.302423},
volume = {212},
year = {2019}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Mitochondrial DNA (mtDNA) mutations cause severe congenital diseases but may also be associated with healthy aging. MtDNA is stochastically replicated and degraded, and exists within organelles which undergo dynamic fusion and fission. The role of the resulting mitochondrial networks in the time evolution of the cellular proportion of mutated mtDNA molecules (heteroplasmy), and cell-to-cell variability in heteroplasmy (heteroplasmy variance), remains incompletely understood. Heteroplasmy variance is particularly important since it modulates the number of pathological cells in a tissue. Here, we provide the first wide-reaching theoretical framework which bridges mitochondrial network and genetic states. We show that, under a range of conditions, the (genetic) rate of increase in heteroplasmy variance and de novo mutation are proportionally modulated by the (physical) fraction of unfused mitochondria, independently of the absolute fission-fusion rate. In the context of selective fusion, we show that intermediate fusion/fission ratios are optimal for the clearance of mtDNA mutants. Our findings imply that modulating network state, mitophagy rate and copy number to slow down heteroplasmy dynamics when mean heteroplasmy is low could have therapeutic advantages for mitochondrial disease and healthy aging.
AU - Aryaman,J
AU - Bowles,C
AU - Jones,NS
AU - Johnston,IG
DO - 10.1534/genetics.119.302423
EP - 1443
PY - 2019///
SN - 0016-6731
SP - 1429
TI - Mitochondrial network state scales mtDNA genetic dynamics
T2 - Genetics
UR - http://dx.doi.org/10.1534/genetics.119.302423
UR - https://www.ncbi.nlm.nih.gov/pubmed/31253641
UR - http://hdl.handle.net/10044/1/72727
VL - 212
ER -