Mitochondrial Diseases as Model of Neurodegeneration

Abstract

"Mitochondria" partially autonomous sophisticated cellular organelle involved in a wide range of crucial cellular functions, well known as the power house of the cell where ATP (adenosine triphosphate) production takes place, that is the cellular source of energy.Mitochondria has its own genome, however proper functioning of the mitochondria is dependent upon the coordinated expression of both nuclear and mitochondrial encoded gene products. Peculiar maternal inheritance of mitochondrial DNA has led the scientists to think about mitochondrial donation as a solution to maternally inherited mitochondriopathy "Three parent baby", raising many ethical and scientific issues, concerns about safety of the procedure, long term outcome and effect of genetic modification are still questionable.Mitochondrial DNA has a higher mutation rate compared to nuclear DNA. Mitochondrial research has revealed a lot about methods of its DNA repair emphasizing the role of nuclear encoded products in this process.Mitochondrial diseases are clinically and genetically diverse, fortunately next generation sequencing (NGS) technologies have made a breakthrough in mitochondrial disorders, the whole mitochondrial genome has been sequenced with more than 250 nuclear encoded genes associated with mitochondrial syndromes identified to date, It unraveled the role of mitochondrial disorders in neurodegenerative disorders. However many pathogenic candidate genes remain uncharacterized even with whole exome sequencing (WES).In this chapter here we handle cases with various neurodegenerative diseases that have been genetically diagnosed thanks to NGS, revealing the role of mitochondrial dysfunction in neurodegeneration, offering a therapeutic target for these handicapping disorders.

Mitochondrial Molecular Abnormalities Revealed by Proteomic Analysis of Hippocampal Organelles of Mice Triple Transgenic for Alzheimer Disease

“…Mounting evidence suggests that mitochondrial dysfunction is closely related to the pathogenesis of several neurodegenerative disorders, including AD (Müller et al, 2010 ; Calkins et al, 2011 ; Selim and Hassaan, 2017 ; Weng et al, 2017 ). Mitochondrial dysfunction is mainly manifested as an energy metabolism disorder, ETC damage, mitochondrial dynamics disorder and related descriptors (Minoshima et al, 1997 ; Etminan et al, 2005 ; Chan, 2006b ; Aung et al, 2017 ).…”

Polycystic ovary syndrome and mitochondrial dysfunction

“…Defects in mitochondrial DNA replication result in mtDNA mutation, multiple deletions, and mtDNA molecule depletion [46]. Moreover, mtDNA has a higher mutation rate than nuclear DNA because it lacks histone protection and a DNA damage repair system and approaches the electron transport chain (ETC) system, which produces oxygen-free radicals [47]. Existing studies have shown that mtDNA mutations contribute to many diseases, such as PCOS.…”

Mitochondrial Dysfunction in Polycystic Ovary Syndrome

“…Due to the unique structural properties of mitochondrial genes, the frequency of DNA mutations is much higher than that of nuclear DNA (Selim and Hassaan, 2017). Recent studies have shown a positive correlation between mitochondrial dysfunction and PCOS, and PCOS-IR mitochondrial genome mutations have become a research hotspot (Table 1).…”