Mitochondrial heteroplasmy beyond the oocyte bottleneck

Semin Cell Dev Biol. 2020 Jan;97:156-166. doi: 10.1016/j.semcdb.2019.10.001. Epub 2019 Oct 11.

Abstract

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, mutations in the mtDNA 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 are the cause of severe progressive mitochondrial disorders and play 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.

Keywords: Bottleneck; Heteroplasmy; Mitochondrial genome; Paternal leakage; Recombination; Somatic segregation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Female
  • Humans
  • Mitochondria / metabolism*
  • Oocytes / metabolism*