Abstract
Mitochondrial replacement therapy, a procedure to generate embryos with the nuclear genome of a donor mother and the healthy mitochondria of a recipient egg, has recently emerged as a promising strategy to prevent transmission of devastating mitochondrial DNA diseases and infertility. The procedure may produce an embryo that is free of diseased mitochondria. A recent study addresses important fundamental questions about the mechanisms underlying maternal inheritance and translational questions regarding the transgenerational effectiveness of this promising therapeutic strategy. This review considers recent advances in our understanding of maternal inheritance of mitochondria, implications for fertility and mitochondrial disease, and potential roles for the Balbiani body, an ancient oocyte structure, in mitochondrial selection in oocytes, with emphasis on therapies to remedy mitochondrial disorders.
Highlights
Mitochondrial replacement therapy, a procedure to generate embryos with the nuclear genome of a donor mother and the healthy mitochondria of a recipient egg, has recently emerged as a promising strategy to prevent transmission of devastating mitochondrial DNA diseases and infertility
The mitochondrial genome of humans is comprised of 37 genes that encode the tRNAs and ribosomal RNA required to translate the proteins of the electron transport chain as well as proteins that are necessary for oxidative phosphorylation
The mitochondrial genome is not transmitted by sexual reproduction, but instead in most animals mitochondria are strictly inherited from one parent, usually the mother
Summary
Modern eukaryotic cells coevolved in a symbiotic relationship that began between microorganisms, archaebacteria and ancestral mitochondria two billion years ago. A heteroplasmic mother, an individual with more than one type of mitochondria due to accumulation of mutations, can produce progeny with only the mutant mitochondrial DNA (homoplasmic) Such enrichment of mutant mitochondria indicates the existence of a mitochondrial bottleneck. According to the stochastic or “mitotic segregation” mechanism, a heteroplasmic cell can generate progeny with distinct mitochondrial DNA composition over a short time, depending on the extent to which mitochondrial DNA replication occurs before or after the cell divides. According to this model, most cells in a heteroplasmic individual would be expected to have a random distribution of normal and potentially pathogenic mitochodria. An alternative possibility, based on examination of heteroplasmic mice, indicates that variation from cell to cell in a heteroplasmic individual may not be stochastic, but is influenced by tissue specific mechanisms or bottlenecks that drive mitochondria selection [25]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
