Mitochondrial MicroRNAs in Aging and Neurodegenerative Diseases

Abstract

MicroRNAs (miRNAs) are important regulators of several biological processes, such as cell growth, cell proliferation, embryonic development, tissue differentiation, and apoptosis. Currently, over 2000 mammalian miRNAs have been reported to regulate these biological processes. A subset of microRNAs was found to be localized to human mitochondria (mitomiRs). Through years of research, over 400 mitomiRs have been shown to modulate the translational activity of the mitochondrial genome. While miRNAs have been studied for years, the function of mitomiRs and their role in neurodegenerative pathologies is not known. The purpose of our article is to highlight recent findings that relate mitomiRs to neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's. We also discuss the involvement of mitomiRs in regulating the mitochondrial genome in age-related neurodegenerative diseases.

Keywords: Alzheimer’s disease; Huntington’s disease; Parkinson’s disease; aging; microRNAs; mitochondrial function and mitophagy; mitochondrial microRNAs; oxidative stress.

Figure 1

Mitochondrial structure. Schematic of the mitochondrion showing the electron transport chain, flow of ions, and generation reactive oxidative species. These reactive oxidative species can be reduced to hydrogen peroxide via the SOD2 enzyme and further broken down into H₂O and O₂ by the GPX enzyme. However, the reduction process is not perfect and when under high stress, reactive oxidative species can leak out of the mitochondria. The mitochondria are also important regulators of intracellular calcium concentration.

Figure 2

Production and import of mitomiRNA.

Figure 3

Demonstrates oxidative stress in aging and other age-related diseases. A healthy cell can balance the production of reactive oxidative species and antioxidant enzymes. However, in disease states, such as Alzheimer’s, Parkinson’s, a combination of increased levels of reactive oxidative species production and decreased antioxidant enzymes production have been observed. This imbalance is known as oxidative stress, observed in a large number of human diseases.