MATERNAL mtDNA INHERITANCE: SPERM CELLS' MITOCHONDRIA ALMOST LACK DNA

 

For more than a century, mitochondria have been a focal point of research across various branches of experimental biology. In the last 30 years, they have gained particular significance in different disciplines. To cytologists, mitochondria served as ideal subjects for exploring cellular ultrastructure using electron microscopy and developing tissue-fractionation techniques to isolate organelles. Biochemists found mitochondria crucial as the site of cell respiration, marking a pivotal step in understanding and reconstructing these processes at a molecular level, especially about cellular membranes. Physiologists seized the opportunity provided by mitochondria to investigate structure-function relationships, particularly in active transport, vectorial metabolism, and subcellular metabolic control mechanisms. Meanwhile, molecular biologists were intrigued by the revelation of mitochondrial DNA, protein synthesis, and the exploration of mitochondrial biogenesis, ushering in a new era in the understanding of eukaryotic gene expression.

Simply Mitochondria are cellular organelles enclosed by membranes. They play a crucial role in producing most of the chemical energy required to fuel the biochemical processes within the cell. The energy generated by mitochondria is stored in a compact molecule known as adenosine triphosphate (ATP).

Researchers have long acknowledged that human mitochondrial DNA (mtDNA) is solely inherited from egg cells, with only the mother contributing the genetic code carried by numerous mitochondria crucial for cellular energy production. Previous assumptions suggested that paternal mtDNA was eradicated shortly after sperm fused with an egg during fertilisation, potentially through an immune-like search-and-destroy mechanism. However, the study revealed that although mature sperm contain a limited number of mitochondria, these lack intact mtDNA.

Mitochondrial DNA (mtDNA) exhibits uniparental inheritance in the majority of eukaryotes, a trait evolutionarily conserved. In various species, including humans, the introduction of sperm mitochondria to the oocyte during fertilization occurs. The proposed mechanisms preventing the transmission of paternal mtDNA involve ubiquitination of sperm mitochondria and mitophagy. However, the specific causative mechanisms underlying paternal mtDNA elimination remain undefined. The investigation revealed that mitochondria in human spermatozoa lack intact mtDNA and the essential nucleoid protein, mitochondrial transcription factor A (TFAM), crucial for protecting, maintaining, and transcribing mtDNA. During spermatogenesis, sperm cells express a TFAM isoform that retains the mitochondrial presequence, typically removed upon mitochondrial import. Phosphorylation of this presequence prevents mitochondrial import, directing TFAM to the nucleus of the spermatozoon. The relocalization of TFAM from the mitochondria of spermatogonia to the spermatozoa nucleus correlates directly with mtDNA elimination, elucidating the maternal inheritance pattern observed in this species.

REFERENCE

Lee W, Zamudio-Ochoa A, Buchel G, Podlesniy P, Marti Gutierrez N, Puigròs M, et al. Molecular basis for maternal inheritance of human mitochondrial DNA. Nature Genetics. 2023;55(10):1632–9. doi:10.1038/s41588-023-01505-9