Folk Nature

Uniparental Inheritance of Mitochondrial DNA (mtDNA)

Uniparental inheritance of mitochondrial DNA (mtDNA) is a captivating evolutionary trait observed across nearly all eukaryotic organisms. This unique phenomenon, which entails the exclusive transmission of mtDNA from one parent, has intrigued the scientific community for decades. In this article, we embark on a journey to comprehend the mechanisms behind this captivating process, particularly in humans.

The Puzzle of Paternal mtDNA Transmission

In numerous species, including humans, the male contribution to reproduction introduces sperm mitochondria to the oocyte during fertilization. This raises a fundamental question: How is paternal mtDNA transmission prevented? Scientists have proposed several mechanisms, such as ubiquitination of sperm mitochondria and mitophagy, but the causative mechanisms have remained elusive.

The Missing Elements: TFAM and Mitochondrial Integrity

Recent research has illuminated this enigma. Scientists have unearthed a critical clue in the form of mitochondrial transcription factor A (TFAM). TFAM is a major nucleoid protein responsible for safeguarding, sustaining, and transcribing mtDNA. Surprisingly, in human spermatozoa, mitochondria are found to lack intact mtDNA and TFAM.

The Role of TFAM Isoform

During spermatogenesis, an extraordinary process unfolds. Sperm cells express an isoform of TFAM that retains the mitochondrial presequence. Normally, this presequence is removed upon mitochondrial import. However, phosphorylation of this presequence takes an exceptional turn—it obstructs mitochondrial import and redirects TFAM to the spermatozoon nucleus.

TFAM Relocalization and mtDNA Elimination

The key revelation lies in TFAM relocalization. As TFAM relocates from the mitochondria of spermatogonia to the spermatozoa nucleus, it directly correlates with the elimination of mtDNA. This discovery offers a compelling explanation for maternal inheritance of mtDNA in humans.

Access to Research Data

It’s crucial to note that this research is accompanied by invaluable source data. Mass spectrometry proteomics data can be accessed through the MassIVE and ProteomeXchange data repositories. Additionally, mitochondrial and nuclear DNA sequencing read counts, vital for mtDNA copy number inference, are included in Supplementary Table 1.

Protecting Research Participants’ Privacy

Ethical considerations are of paramount importance in clinical research. In alignment with international laws and OHSU IRB regulations, preserving the anonymity of research participants is a fundamental ethical requirement. To shield participants’ privacy, data disclosing genetic identity-related information cannot be publicly shared beyond the OHSU network.

Requesting Access

Researchers interested in accessing this data can initiate a request through OHSU Research Integrity. The process, guided by OHSU compliance officers, ensures confidentiality. Successful approval grants access to an OHSU computer in a secure office, where researchers can review the whole-genome sequencing datasets.

For access requests or further inquiries, please contact Kara Drolet, Associate VP, ORIO, at irb@ohsu.edu.

Conclusion

The mystery of uniparental inheritance of mtDNA in humans is elucidated, thanks to pioneering research on TFAM and its role in redefining the destiny of mitochondrial DNA. This discovery not only contributes to our comprehension of evolutionary biology but also underscores the significance of safeguarding research participants’ privacy and facilitating responsible data access.

Source:

Oregon Health & Science University

Journal reference:

Lee, W., et al. (2023) Molecular basis for maternal inheritance of human mitochondrial DNA. Nature Geneticsdoi.org/10.1038/s41588-023-01505-9.

FAQs (Frequently Asked Questions)

What is uniparental inheritance of mitochondrial DNA (mtDNA)?

Uniparental inheritance signifies the exclusive transmission of mtDNA from one parent, typically the mother, in eukaryotic organisms.

How is paternal mtDNA transmission prevented in humans?

Recent research has disclosed that paternal mtDNA transmission is averted through the relocalization of mitochondrial transcription factor A (TFAM) from sperm mitochondria to the spermatozoon nucleus.

Where can researchers access the source data related to this research?

Mass spectrometry proteomics data is accessible in the MassIVE and ProteomeXchange data repositories, while mitochondrial and nuclear DNA sequencing read counts are provided in Supplementary Table 1.

What ethical considerations are taken into account in this research?

Safeguarding the privacy of research participants is the top priority. Data revealing the genetic identity of gamete donors is not publicly shared, ensuring confidentiality.

How can researchers request access to the research data?

Researchers interested in accessing the data should contact Kara Drolet, Associate VP, ORIO, at irb@ohsu.edu, and follow the established process, which prioritizes responsible and controlled data access.

Leave a Comment