Author(s):
Shipra Sharma

Abstract:
Mitochondria, often referred to as the powerhouse of the cell, predominantly influence highly energy-dependent organs such as the brain, heart, and skeletal muscles. Consequently, mitochondrial disorders are commonly classified as encephalocardiomyopathies. These disorders typically involve multiple organ systems, with neurological dysfunction being one of the most prominent clinical features. The interplay between mitochondrial DNA and nuclear DNA adds another layer of complexity to understanding and diagnosing mitochondrial disorders. Furthermore, clinical heterogeneity—where a single mutation may lead to diverse phenotypes and similar phenotypes with various mutations may arise from different genetic defects—significantly complicates diagnosis. Another major challenge arises from the highly polymorphic nature of the mitochondrial genome, largely attributed to its exposure to a highly oxidative environment. As a result, distinguishing pathogenic or deleterious variants from benign polymorphisms becomes difficult, necessitating the use of specific criteria and computational prediction algorithms. Despite these challenges, substantial progress has been made in recent years. An increasing number of nuclear genes associated with mitochondrial dysfunction have been identified, enriching our understanding of disease mechanisms. The advent of next-generation sequencing (NGS) has further accelerated the field by enabling comprehensive analysis of both mitochondrial and nuclear genomes in a single workflow. This review focuses on the role of mitochondrial polymorphisms in the pathogenesis of major neurological disorders. Recent advancements in genetics and genomics are significantly improving our understanding of mitochondrial disease complexity and are paving the way for more accurate diagnosis and potential therapeutic strategies.

Pages: 899-916

Read Full Article