Review

Department of Pathology & Laboratory Medicine, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 3K7, Canada

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Quinn Le

https://orcid.org/0009-0004-7058-1629

Department of Pathology & Laboratory Medicine, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 3K7, Canada

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Phyo W Win

https://orcid.org/0009-0000-2761-0800

Department of Pathology & Laboratory Medicine, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 3K7, Canada

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Kathleen A Hill

https://orcid.org/0000-0002-7788-5105

Department of Biology, Western University, London, ON, N6A 3K7, Canada

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Shiva M Singh

https://orcid.org/0000-0003-2956-7679

Department of Biology, Western University, London, ON, N6A 3K7, Canada

Children's Health Research Institute, Lawson Research Institute, London, ON, N6C 2R5, Canada

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Christina A Castellani

*Author for correspondence:

E-mail Address: christina.castellani@schulich.uwo.ca

https://orcid.org/0000-0003-2737-0549

Department of Pathology & Laboratory Medicine, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 3K7, Canada

Department of Epidemiology & Biostatistics, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 3K7, Canada

Children's Health Research Institute, Lawson Research Institute, London, ON, N6C 2R5, Canada

McKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

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Published Online:21 Nov 2023https://doi.org/10.2217/epi-2023-0322

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Abstract

Bidirectional communication between the mitochondria and the nucleus is required for several physiological processes, and the nuclear epigenome is a key mediator of this relationship. ncRNAs are an emerging area of discussion for their roles in cellular function and regulation. In this review, we highlight the role of mitochondrial-encoded ncRNAs as mediators of communication between the mitochondria and the nuclear genome. We focus primarily on retrograde signaling, a process in which the mitochondrion relays ncRNAs to translate environmental stress signals to changes in nuclear gene expression, with implications on stress responses that may include disease(s). Other biological roles of mitochondrial-encoded ncRNAs, such as mitochondrial import of proteins and regulation of cell signaling, will also be discussed.

Plain language summary

Communication between the nucleus (the cell control center) and the mitochondria (the energy-producing factories of the cell) is important for keeping cells working properly. Though communication goes both ways, signals sent from the mitochondria to the nucleus have become a big topic of discussion because they have been found to affect disease. ncRNAs are another topic that has been gaining traction. These are RNA transcripts that, instead of coding for proteins, have other roles in controlling our cells. Here we discuss ncRNAs that come from the mitochondria, called mt-ncRNAs. By sending mt-ncRNAs to the nucleus, mitochondria can send messages to the nucleus to help cells adapt to stress or changes in the environment. These mt-ncRNAs demonstrate the importance of mitochondria in controlling our cells. By studying this process, we gain information that helps in treating diseases.

Tweetable abstract

The emerging role of mitochondrial-encoded ncRNAs as mediators of the mitochondrial–nuclear signaling pathway, eliciting adaptive nuclear gene expression changes in response to environmental stress.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 15, No. 21

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Received 8 September 2023

Accepted 30 October 2023

Published online 21 November 2023

Published in print November 2023

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Acknowledgments

We thank E Shin for assistance with proofreading of the final manuscript.

Financial disclosure

This work was supported by funding from The Department of Pathology and Laboratory Medicine at Western University (C Castellani), The Natural Sciences and Engineering Research Council of Canada (S Singh, K Hill), the Ontario Graduate Scholarship (P Win) and Undergraduate Student Research Internship support from Western University (C Castellani, J Nguyen).

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

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Decoding mitochondrial–nuclear (epi)genome interactions: the emerging role of ncRNAs

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