FIGURE 4.

A schematic diagram of mtDNA methylation and the bidirectional communication between mitochondria and nuclear in epigenetic regulation. Mitochondria maintain their homeostasis in several ways including mitochondrial biogenesis, dynamic, mitophagy and apoptosis. Disruption of mitochondrial homeostasis will result in impaired mitochondrial function, which may contribute to neurodegenerative diseases. Mitochondria are involved in the epigenetic regulation from two aspects. One is mtDNA methylation, the extent of which varies among neurodegenerative diseases. The other is the bidirectional communication between mitochondria and nuclear, which is essential to maintain mitochondria homeostasis and can play a role in nuclear epigenetic regulation of neurogenerative diseases. Acetyl-CoA and NAD⁺ provided by mitochondria indirectly play a role in histone acetylation and deacetylation, respectively, to influencing mitochondria homeostasis. Mitochondria can influence the production of SAM that regulated nuclear DNA methylation. On the other hand, non-coding RNAs coded by nuclear genome can regulate neurogenerative diseases by influencing mitochondria homeostasis. Dashed arrows indicate pathways that need further validation. Abbreviations: PCAD, preclinical Alzheimer’s disease; LAD, late-stage Alzheimer’s disease; LOAD late-onset Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; and SAM, S-adenosyl methionine.