“Overall, Dr. Prakash’s team has synthesized an important body of work that will inform the research community about the current state of knowledge in the area of influences on mitochondrial DNA as well as critical knowledge gaps,” said Caren Weinhouse, Ph.D., editor of the peer-reviewed journal.
Often referred to as “the powerhouse of the cell,” Weinhouse said, mitochondria are the cellular organelles responsible for generating cellular energy in the form of adenosine triphosphate, or ATP. Because the ancestral mitochondrion was a bacterial cell that was engulfed by another cell, mitochondria contain their own DNA molecules, distinct from nuclear DNA.
In this review, Weinhouse said, Prakash and co-authors Nidhi Sharma and Monica S. Pasala summarize the existing data on mitochondrial replication, transcription and repair, including highlighting the subset of base excision repair-initiating DNA glycosylases present in mitochondria, which are critical for maintaining the integrity of DNA molecules that are situated so nearby the electron transport chain, which produces significant amounts of reactive oxygen species. Sharma is a postdoctoral fellow in Prakash’s lab while Pasala was a student who previously worked with Prakash at the USA College of Medicine and MCI.
Notably, the authors discuss the controversial detection of covalent modifications to mitochondrial DNA, including 5-methylcytosine, the most common form of DNA methylation in mammalian nuclear DNA, and 6-methyladenine, a common modification of DNA in bacteria, including those ancestral to mitochondria, Weinhouse said.
The research article also details current evidence for other potential epigenetic mechanisms of mitochondrial gene regulation, including those that function via non-coding RNA or post-translational modifications to mitochondrial nucleoids, which are the mitochondrial structural, and perhaps functional, equivalent of nuclear nucleosomes. The review concludes by highlighting open questions on transcriptional regulation in mitochondria, as well as the presence and function of epigenetic modifications to mitochondrial DNA and associated proteins.
Prakash joined the USA College of Medicine and USA Health Mitchell Cancer Institute in 2016 as an assistant professor after completing post-doctoral research at the University of Vermont. Her work focuses on DNA repair mechanisms in the mitochondria. She earned a Ph.D. in cancer research at the University of Nebraska Medical Center and received specialized training in crystallography at Brookhaven National Labs in Long Island, N.Y.
