Mitochondrial heteroplasmy beyond the oocyte bottleneck.
Seminars in cell & developmental biology
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Van Den Ameele, J., Li, A. Y., Ma, H., & Chinnery, P. (2020). Mitochondrial heteroplasmy beyond the oocyte bottleneck.. Seminars in cell & developmental biology, 97 156-166. https://doi.org/10.1016/j.semcdb.2019.10.001
Inheritance of the mitochondrial genome does not follow the rules of conventional Mendelian genetics. The mitochondrial DNA (mtDNA) is present in many copies per cell and is inherited through the maternal germline. In addition, novel mutations will give rise to heteroplasmy, the coexistence of different mtDNA variants within a single cell, whose levels can vary considerably between cells, organs or organisms. The inheritance and subsequent accumulation of deleterious variants of mtDNA is the cause of severe progressive mitochondrial disorders and plays a role in many other conditions, including aging, cancer and neurodegenerative disorders. Here, we discuss the processes that give rise to cell-to-cell variability in mtDNA composition, focussing on somatic mtDNA segregation and on less conventional sources of heteroplasmy: non-maternal inheritance and mtDNA recombination. Understanding how mtDNA variants and mutations emerge and evolve within an organism is of crucial importance to prevent and cure mitochondrial disease and can potentially impact more common aging-associated conditions.
EMBO Long-term Fellowship (ALTF 1600_2014) Wellcome Trust Postdoctoral Training Fellowship for Clinicians (105839). Wellcome Trust Sir Henry Dale Fellow (202269/Z/16/Z) Wellcome Trust Principal Research Fellow (212219/Z/18/Z) UK NIHR Senior Investigator Support from the Medical Research Council Mitochondrial Biology Unit (MC_UP_1501/2), the Evelyn Trust, and the National Institute for Health Research (NIHR) Biomedical Research Centre
Wellcome Trust (202269/Z/16/Z)
WELLCOME TRUST (105839/Z/14/Z)
Wellcome Trust (212219/Z/18/Z)
External DOI: https://doi.org/10.1016/j.semcdb.2019.10.001
This record's URL: https://www.repository.cam.ac.uk/handle/1810/297429
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/