The October 2019 Editor's Choice article is "Mitochondrial DNA: Epigenetics and Environment" (https://onlinelibrary.wiley.com/doi/10.1002/em.22319) by Nidhi Sharma, Monica S. Pasala, and Aishwarya Prakash.
Often referred to as “the powerhouse of the cell,” 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. Mitochondrial DNA structure and function reflects its bacterial origins; mitochondrial DNA is a circular molecule that encodes polycistronic transcripts, the DNA is organized into simple nucleoprotein complexes, rather than the complex chromatin structures observed with nuclear DNA. However, because the nuclear DNA encodes the majority of mitochondrial proteins, and because the cell relies on mitochondrial function, effective crosstalk between these compartments, including responsive transcriptional regulatory circuits, is critical to cellular homeostasis.
In this review, Dr. Prakash and co-authors 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. 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. The authors also discuss 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.
Overall, Dr. Prakash’s team has synthesized an important body of work that will inform the research community about the current state of knowledge, as well as critical knowledge gaps, in the area of environmental influences on mitochondrial DNA.
Environ Mol Mutagen 60:668-682, 2019. © 2019 Wiley Periodicals, Inc.