MitochondrialDNA: Fate of the Paternal Mitochondrial Genome

Abstract

AbstractThe 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 thus maternally inherited. Sperm mitochondrial deoxyribonucleic acid (mtDNA) is normally eliminated early during embryonic development, but this tends to be species specific. There are several interconnected mechanisms that could account for its elimination, including ubiquitin depended proteolysis, mtDNA digestion by a dedicated endonuclease and whole organelle autophagy/mitophagy. The elimination of sperm mitochondrial DNA is essential for the functional integrity of the embryo, and for the health, fitness and fertility of the offspring. Sperm mtDNA appears to harbour a large number of defects, whereas maternally inherited mitochondrial DNA rearrangements appear to be transmitted at a very low frequency. However, there is an increasing number of assisted reproductive technologies and therapies that could lead to the transmission of paternal/foreign mitochondrial DNA and this requires significant investigation.Key ConceptsMitochondria are semi‐autonomous energy‐producing organelles with their own genome (mitochondrial DNA/mtDNA) and transcriptional and translational machinery.Mitochondrial health influences fitness, health and fertility in humans and animals.In most animals and in humans, mitochondria and mitochondrial genomes are inherited clonally, from mother (the concept of ‘mitochondrial Eve’), though exceptions exist.Paternal mitochondria enter the oocyte at fertilisation but are eliminated soon thereafter by the ooplasmic autophagy/mitophagy machinery.Sperm‐borne (paternal) mitochondria are predestined for proteolysis and mitophagy as they are tagged with the recycling marker ubiquitin during the haploid phase of spermatogenesis.Elimination of paternal mitochondria is essential for an individual's health as it prevents the transmission of harmful mtDNA mutations and deletions.Paternal mitochondrial heteroplasmy caused by the leakage/recycling failure of sperm mitochondria after fertilisation has been associated with mitochondrial disease in humans.Some assisted reproductive therapies (ART) such as intracytoplasmic sperm injection (ICSI) may be liable to convey paternal mitochondrial leakage, though there is no consistent screening for it ART children.