From powerhouse to regulator: The role of mitoepigenetics in mitochondrion-related cellular functions and human diseases

Luigi Donato; Domenico Mordà; Concetta Scimone; Simona Alibrandi; Rosalia D'Angelo; Antonina Sidoti

doi:10.1016/j.freeradbiomed.2024.03.025

From powerhouse to regulator: The role of mitoepigenetics in mitochondrion-related cellular functions and human diseases

Free Radic Biol Med. 2024 Mar 31:218:105-119. doi: 10.1016/j.freeradbiomed.2024.03.025. Online ahead of print.

Authors

Luigi Donato¹, Domenico Mordà², Concetta Scimone³, Simona Alibrandi⁴, Rosalia D'Angelo⁵, Antonina Sidoti⁶

Affiliations

¹ Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, 98122, Messina, Italy; Department of Biomolecular Strategies, Genetics, Cutting-Edge Therapies, Euro-Mediterranean Institute of Science and Technology (I.E.ME.S.T.) 90139 Palermo, Italy. Electronic address: ldonato@unime.it.
² Department of Biomolecular Strategies, Genetics, Cutting-Edge Therapies, Euro-Mediterranean Institute of Science and Technology (I.E.ME.S.T.) 90139 Palermo, Italy; Department of Veterinary Sciences, University of Messina, 98122, Messina, Italy. Electronic address: domenico.morda@studenti.unime.it.
³ Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, 98122, Messina, Italy; Department of Biomolecular Strategies, Genetics, Cutting-Edge Therapies, Euro-Mediterranean Institute of Science and Technology (I.E.ME.S.T.) 90139 Palermo, Italy. Electronic address: cscimone@unime.it.
⁴ Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, 98122, Messina, Italy; Department of Biomolecular Strategies, Genetics, Cutting-Edge Therapies, Euro-Mediterranean Institute of Science and Technology (I.E.ME.S.T.) 90139 Palermo, Italy. Electronic address: salibrandi@unime.it.
⁵ Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, 98122, Messina, Italy. Electronic address: rdangelo@unime.it.
⁶ Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, 98122, Messina, Italy. Electronic address: asidoti@unime.it.

PMID: 38565400
DOI: 10.1016/j.freeradbiomed.2024.03.025

Abstract

Beyond their crucial role in energy production, mitochondria harbor a distinct genome subject to epigenetic regulation akin to that of nuclear DNA. This paper delves into the nascent but rapidly evolving fields of mitoepigenetics and mitoepigenomics, exploring the sophisticated regulatory mechanisms governing mitochondrial DNA (mtDNA). These mechanisms encompass mtDNA methylation, the influence of non-coding RNAs (ncRNAs), and post-translational modifications of mitochondrial proteins. Together, these epigenetic modifications meticulously coordinate mitochondrial gene transcription, replication, and metabolism, thereby calibrating mitochondrial function in response to the dynamic interplay of intracellular needs and environmental stimuli. Notably, the dysregulation of mitoepigenetic pathways is increasingly implicated in mitochondrial dysfunction and a spectrum of human pathologies, including neurodegenerative diseases, cancer, metabolic disorders, and cardiovascular conditions. This comprehensive review synthesizes the current state of knowledge, emphasizing recent breakthroughs and innovations in the field. It discusses the potential of high-resolution mitochondrial epigenome mapping, the diagnostic and prognostic utility of blood or tissue mtDNA epigenetic markers, and the promising horizon of mitochondrial epigenetic drugs. Furthermore, it explores the transformative potential of mitoepigenetics and mitoepigenomics in precision medicine. Exploiting a theragnostic approach to maintaining mitochondrial allostasis, this paper underscores the pivotal role of mitochondrial epigenetics in charting new frontiers in medical science.

Keywords: Epigenetic biomarkers; Mitochondrial dysfunction; Mitochondrial therapy; Mitoepigenetics; Mitoepigenomics; Precision medicine.

Publication types

Review