TY - JOUR

T1 - Natural and artificial mechanisms of mitochondrial genome elimination

AU - Zakirova, Elvira G.

AU - Muzyka, Vladimir V.

AU - Mazunin, Ilya O.

AU - Orishchenko, Konstantin E.

N1 - Funding Information: Funding: This work was supported by the Ministry of Education and Science of Russian Federation, grant number 2019-0546 (FSUS-2020-0040) and by the RFBR grant number 19-34-90087. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/2

Y1 - 2021/2

N2 - The generally accepted theory of the genetic drift of mitochondrial alleles during mammalian ontogenesis is based on the presence of a selective bottleneck in the female germline. However, there is a variety of different theories on the pathways of genetic regulation of mitochondrial DNA (mtDNA) dynamics in oogenesis and adult somatic cells. The current review summarizes present knowledge on the natural mechanisms of mitochondrial genome elimination during mammalian development. We also discuss the variety of existing and developing methodologies for artificial manipulation of the mtDNA heteroplasmy level. Understanding of the basics of mtDNA dynamics will shed the light on the pathogenesis and potential therapies of human diseases associated with mitochondrial dysfunction.

AB - The generally accepted theory of the genetic drift of mitochondrial alleles during mammalian ontogenesis is based on the presence of a selective bottleneck in the female germline. However, there is a variety of different theories on the pathways of genetic regulation of mitochondrial DNA (mtDNA) dynamics in oogenesis and adult somatic cells. The current review summarizes present knowledge on the natural mechanisms of mitochondrial genome elimination during mammalian development. We also discuss the variety of existing and developing methodologies for artificial manipulation of the mtDNA heteroplasmy level. Understanding of the basics of mtDNA dynamics will shed the light on the pathogenesis and potential therapies of human diseases associated with mitochondrial dysfunction.

KW - Heteroplasmy

KW - Mitochondrial DNA segregation

KW - Mitochondrial engineered nucleases

KW - Mitophagy

KW - Selective elimination

UR - http://www.scopus.com/inward/record.url?scp=85099919676&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/60115f3f-eca8-3b8f-9be5-70e2cec0eda9/

U2 - 10.3390/life11020076

DO - 10.3390/life11020076

M3 - Review article

C2 - 33498399

AN - SCOPUS:85099919676

VL - 11

SP - 1

EP - 22

JO - Life

JF - Life

SN - 2075-1729

IS - 2

M1 - 76

ER -