Mitochondrial DNA: Fate of the Paternal Mitochondrial Genome


The mitochondrial genome encodes key proteins of the electron transfer chain, which generates the vast majority of cellular adenosine triphosphate through oxidative phosphorylation. This genome is normally transmitted to subsequent generations through the oocyte and is maternally inherited. Sperm mitochondrial deoxyribonucleic acid (DNA) is normally eliminated early during embryonic development, but this tends to be species specific. There are several mechanisms that could account for its elimination. The elimination of sperm mitochondrial DNA is essential for the functional integrity of the offspring, as sperm mitochondrial DNA appears to harbour a large number of mitochondrial DNA defects, whereas maternally inherited mitochondrial DNA rearrangements appear to be transmitted at a very low frequency. However, there are an increasing number of assisted reproductive technologies that could lead to the transmission of sperm mitochondrial DNA and this requires significant investigation.

Key Concepts:

  • Mitochondrial DNA is predominantly maternally inherited.

  • In some species, there is either leakage or directed transmission of sperm mitochondrial DNA.

  • Elimination of sperm mitochondrial DNA is essential for maintaining the health of the individual.

  • It still remains to be determined how sperm mitochondrial DNA is eliminated and whether this is truly a targeted process.

  • The role of sperm mtDNA requires determination.

Keywords: mitochondrial DNA; sperm; transmission; replication; elimination

Figure 1.

The mammalian mitochondrial genome. MtDNA is a double‐stranded closed circular genome consisting of a heavy (H) and light (L) strand. The H strand encodes 12 subunits of the electron transfer chain: ND1, ND2, ND3, ND4, ND4L and ND5 (complex I; NADH dehydrogenase); CYTB (complex III); COXI, COXII and COXIII (complex IV); and ATP6 and ATP8 (ATP synthase; complex V). It also encodes the 16‐S and 12‐S ribosomal ribonucleic acids (rRNAs) and 14 transfer RNAs (tRNAs). The L strand encodes one subunit, ND6 (Complex I) and 8 tRNAs. The mtDNA has one noncoding region, the displacement loop (D‐loop), which is the genome's control region that acts as a regulatory region for interaction with the chromosomally encoded transcription and replication factors. It also contains the origin of heavy strand of replication (OH), the heavy (H) and light strand promoters (LSP) and two hypervariable regions, which discriminate between maternal lineages. The origin of light strand replication (OL) is located two‐thirds of the way round the genome. Reproduced from Figure 6.1 in St John . © Springer.

Figure 2.

Replication of mtDNA. Replication of the mitochondrial genome is initiated by TFAM, which generates an RNA–DNA hybrid primer. Replication then proceeds from the origin of heavy strand replication (OH). The double‐stranded mitochondrial genome is unwound by TWINKLE, the mtDNA‐specific helicase. The separated strands are bound by mitochondrial single‐stranded binding proteins (mtSSB) to prevent reannealling prior to completion of replication. The mtDNA polymerase complex comprises the catalytic subunit (POLGA) and two supporting processivity subunits (POLGB). Proofreading is undertaken by the 3′–5′ exonuclease activity within POLGA. Reproduced from Figure 6.3 in St John . © Springer.

Figure 3.

MtDNA copy number during spermatogenesis and spermiogenesis. Spermatogenesis has some requirement for mtDNA in order to generate ATP for motility. Differentiating spermatogonia initially expand their mtDNA copy number then reduce it quite considerably as they differentiate into spermatocytes and spermatids to ensure that as few copies as possible enter the oocyte at fertilisation.

Figure 4.

MtDNA copy number during oogenesis. Mammals inherit mtDNA from the population of mtDNA present in the oocyte at fertilisation. At fertilisation, the mature metaphase‐II oocyte has >200 000 copies of mtDNA and these are derived from approximately 200 copies that are present in primordial germ cells, which are the first identifiable germ cells. In the mouse, these are laid at embryonic day 6.5. Oocytes require >200 000 copies of mtDNA to mediate the process of fertilisation and those oocytes that have <200 000 copies of mtDNA often fail to fertilise or arrest during development.



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Further Reading

Amaral S, Amaral A and Ramalho‐Santos J (2013) Aging and male reproductive function: a mitochondrial perspective. Frontiers in Bioscience (Scholar Edition) 5: 181–197.

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St John JC, Jokhi RP and Barratt CL (2005) The impact of mitochondrial genetics on male infertility. International Journal of Andrology 28: 65–73.

Zhu J, Wang KZ and Chu CT (2013) After the banquet: mitochondrial biogenesis, mitophagy and cell survival. Autophagy 9: 11.

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St. John, Justin C(Dec 2013) Mitochondrial DNA: Fate of the Paternal Mitochondrial Genome. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0006165.pub2]