Mitochondrial Epigenetics: Non-Coding RNAs as a Novel Layer of Complexity

Abstract

Mitochondria are organelles responsible for several functions involved in cellular balance, including energy generation and apoptosis. For decades now, it has been well-known that mitochondria have their own genetic material (mitochondrial DNA), which is different from nuclear DNA in many ways. More recently, studies indicated that, much like nuclear DNA, mitochondrial DNA is regulated by epigenetic factors, particularly DNA methylation and non-coding RNAs (ncRNAs). This field is now called mitoepigenetics. Additionally, it has also been established that nucleus and mitochondria are constantly communicating to each other to regulate different cellular pathways. However, little is known about the mechanisms underlying mitoepigenetics and nuclei–mitochondria communication, and also about the involvement of the ncRNAs in mitochondrial functions and related diseases. In this context, this review presents the state-of-the-art knowledge, focusing on ncRNAs as new players in mitoepigenetic regulation and discussing future perspectives of these fields.

Mitochondrial Transfer in Cancer: A Comprehensive Review

“…Stemness could potentially be included to the list, as (cancer) stem cell mitochondrial metabolism most often differs from that of differentiated (cancer) cells [ 66 ]. While mtDNA encodes only 13 mitochondrial proteins in addition to 22 transfer RNAs and 2 ribosomal RNAs, SNPs, mutations, deletions and/or epigenetic changes (methylation, non-coding RNAs) could convey these traits long-term [ 67 ]. Conversely, gain of function mutations could fade away depending on the half-life of specific mitochondrial components that would directly or indirectly depend on the nuclear DNA expression of donor cells.…”

Mitochondrial Reactive Oxygen Species (ROS) Production Alters Sperm Quality

“…Although the characterization of the mitoRNA landscape in mouse male germ cells, gametes, and zygotes opens the door to novel mechanisms of regulation in mitochondria, much effort is required to unravel the biological functions of these RNAs in germ cell functions and how these molecules may coordinate signalling pathways between nucleus and mitochondria [ 39 ].…”

Functional Foods: An Approach to Modulate Molecular Mechanisms of Alzheimer’s Disease

“…Instead, the level of 5hmC in the mtDNA of AD patients did not change notwithstanding a previous study reported a 5hmC level reduction in aging-associated mtDNA [364]. The discrepancy between Blanch and Dzitoyeva [363,364] studies could be due to the differences between species (humans vs. mice, respectively) and/or the methods used. Dysregulation of mtDNA epigenetic mechanisms could partially explain mitochondrial dysfunction, a recurrent feature of AD [362].…”

“…However, little is known about the mechanisms underlying mitoepigenetics. Blanch et al [363] found a global reduction of 5mC in mtDNA. Analysis of specific loci showed that the levels of 5mC in MT-ND1, a mitochondrial gene encoding a protein of the complex I of the respiratory chain, were lower in the entorhinal cortex of AD patients compared with that in age matched controls.…”