The Mitochondrial Epigenome: a Role in Alzheimer’s Disease?

Abstract

Considerable evidence suggests that mitochondrial dysfunction occurs early in Alzheimer's disease, both in affected brain regions and in leukocytes, potentially precipitating neurodegeneration through increased oxidative stress. Epigenetic processes are emerging as a dynamic mechanism through which environmental signals may contribute to cellular changes, leading to neuropathology and disease. Until recently, little attention was given to the mitochondrial epigenome itself, as preliminary studies indicated an absence of DNA modifications. However, recent research has demonstrated that epigenetic changes to the mitochondrial genome do occur, potentially playing an important role in several disorders characterized by mitochondrial dysfunction. This review explores the potential role of mitochondrial epigenetic dysfunction in Alzheimer's disease etiology and discusses some technical issues pertinent to the study of these processes.

Mitochondrial Dysfunction in Autism Spectrum Disorders

“…These diverse mitochondrial functions coupled with the importance of the mitochondria in the control of cellular energy demands imply that any form of dysfunction could have serious consequences on the health of an individual and may lead to disease. Mitochondrial disease has already been linked to the pathogenesis of diseases such as and Alzheimer's [8].…”

“…Although a regulated level of free radicals is required for key processes such calcium homeostasis, they are capable of attacking important macromolecules such as proteins and lipids, causing cell damage and which can eventually lead to disease. Cell damage caused by ROS is implicated in a number of diseases such as cancer [26,27] and Alzheimer's [8]. Several antioxidant defence mechanisms are employed by the human body to maintain the level of free radicals and regulate the damage they can cause.…”

“…Due to the recent implication of mitochondrial dysfunction in a number of diseases such as Alzheimer's [8,29] and cancer [27], research groups have regained interest in field of mitochondrial genetics and epigenetics. Many processes of mitochondrial gene expression and regulation are, to date, not very well understood.…”

Mitoepigenetics: The different shades of grey

“…This differential methylation was largely limited to the skeletal muscle and spinal cord and well correlated with the mitochondrial loss in the myofibers in the disease pathogenesis. Similarly, mitochondrial epigenetic changes have also been suggested to potentially modulate the pathophysiology of Alzheimer's disease (Devall et al, 2014).…”

A Comparison of Mitochondrial DNA Isolation Methods in Frozen Post-Mortem Human Brain Tissue—Applications for Studies of Mitochondrial Genetics in Brain Disorders

“…Traditional mitochondrial genetic research and, more recently, studies of mitochondrial epigenetics can be hampered by the presence of these nuclear-mitochondrial pseudogenes (NUMTs) as they share a high homology with their mitochondrial paralogs (12, 13). Given the interest in studying mtDNA genetic and epigenetic changes in the pathology of brain diseases characterized by mitochondrial dysfunction, it is imperative that NUMTs are correctly accounted for (14). …”