Mitochondrial anomalies driver to age associated degenerative human ailments

Abstract

Mitochondria play a fundamental role in regulating a variety of complex metabolic processes to maintain adequate energy balance for cellular existence. To orchestrate these functions, an undisturbed mitochondrial dynamics is imperative through a set of tightly guided mechanisms. Interference in key signature processes by several genetic, epigenetic and age-linked factors triggers mitochondrial dysfunction through decrease in mitochondrial biogenesis, reduced mitochondrial content, aberrant mtDNA mutations, increased oxidative stress, deficient mitophagy, energy dysfunction, decrease in anti oxidant defense and impaired calcium homeostasis. Mitochondrial dysfunction is widely implicated in origin and development of various age associated degenerative human ailments including metabolic syndromes, cardiovascular diseases, cancer, diabetes and neurodegenerative disorders. The present review revisits the mitochondrial anomalies involved in aetiology of different human diseases and also highlights the translational significance of nano-vectors aimed for selective mitochondrial engineering which might pave way for development of novel therapeutics.

Mitochondrial Genomic Backgrounds Affect Nuclear DNA Methylation and Gene Expression

“…There are relatively few diseases caused directly by mitochondrial mutations or polymorphisms (38, 39). In most cancers mtDNA polymorphisms are not considered to be ‘drivers’ of tumorigenicity (38, 40, 41).…”

“…In most cancers mtDNA polymorphisms are not considered to be ‘drivers’ of tumorigenicity (38, 40, 41). Rather, they are among many genes influencing disease susceptibility, progression and severity (40–42).…”

Oxidative Stress Triggers Body-Wide Skipping of Multiple Exons of the Spinal Muscular Atrophy Gene

“…OS is linked to several chronic conditions including cancer, cardiovascular diseases and neurodegenerative diseases [ 33 ]. Paraquat (PQ, 1,1′-dimethyl-4,4′-bipyridinium dichloride) is an environmental toxin and OS stimulant that is widely implicated in reactive oxygen species formation and mitochondrial dysfunctions [ 34 – 36 ].…”

Epigenetics: A key paradigm in reproductive health

“…It has been demonstrated that exposure in the parental generation is remembered and transmitted to unexposed future generations through gametes as a "memory" of the environment. Environmental and metabolic conditions during gestation may shape epigenetic reprogramming and may further influence the lifetime health of the child and the disease aetiology in offspring [ 87 88 89 ]. This illustrates that the intrauterine environment (nutrition, stress, and so on) has a vital effect on developmental programming, which, in turn, not only influences the germline (sperm or egg) in the foetus (F1) but also the germline of the foetus (F2) [ 90 ].…”