Mitochondrial Epitranscriptomics: The Role of RNA Modifications in Cellular Energy Regulation and Aging

Mitochondria, often referred to as the powerhouses of the cell, are essential for cellular metabolism and energy production. While their function is primarily regulated by both nuclear and mitochondrial DNA, recent research suggests that modifications to mitochondrial RNA (mtRNA) play a crucial role in shaping mitochondrial activity, maintaining cellular energy balance, and influencing the aging process. This review delves into the emerging field of mitochondrial epitranscriptomics, focusing on key RNA modifications such as N6-methyladenosine (m6A), pseudouridylation, and 5-methylcytosine (m5C), and their role in regulating mitochondrial gene expression and function. We explore how these modifications affect oxidative phosphorylation (OXPHOS), the balance of reactive oxygen species (ROS), and cellular senescence. Additionally, we highlight advanced techniques used to study mitochondrial RNA modifications and examine how their dysregulation is linked to aging and age-related diseases. Finally, we discuss the potential of targeting these modifications for therapeutic interventions. A deeper understanding of mitochondrial epitranscriptomic changes could pave the way for novel approaches to treating neurodegenerative diseases, metabolic disorders, and promoting healthy aging.