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

Abstract

Mohammad Ahmad Ahmad Odah*

Background: Mitochondria play a crucial role in cellular metabolism and energy production. While traditionally studied through nuclear and mitochondrial DNA regulation, recent research highlights the significance of post- transcriptional modifications in mitochondrial RNA (mtRNA). These modifications influence mitochondrial gene expression, energy balance, and aging. Understanding mitochondrial epitranscriptomics—specifically modifications like N6-methyladenosine (m6A), pseudouridylation, and 5-methylcytosine (m5C)—is essential for uncovering their impact on cellular function and disease.

Objective: This review aims to explore the emerging field of mitochondrial epitranscriptomics, analyzing key RNA modifications, their roles in oxidative phosphorylation (OXPHOS) and reactive oxygen species (ROS) regulation, and their implications in aging and age-related diseases. Additionally, we discuss advanced methodologies for studying these modifications and potential therapeutic strategies for mitochondrial dysfunction.

Conclusion: Mitochondrial RNA modifications represent a critical layer of gene regulation affecting cellular energy homeostasis and aging. Their dysregulation is associated with metabolic disorders, neurodegenerative diseases, and cellular senescence. Advances in RNA sequencing and epitranscriptomic research highlight the potential for therapeutic interventions targeting mitochondrial RNA modifications to mitigate mitochondrial dysfunction and promote longevity. A deeper understanding of these modifications could pave the way for novel approaches to treating age-related diseases and enhancing healthy aging.

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