Mitochondrial Dysfunction and Its Impact on Cellular Metabolism in Degenerative Diseases

Neurodegenerative diseases are characterized by the progressive loss of neuronal function and structure and are accompanied by cognitive decline, motor impairment, and behavioral changes. Mitochondrial dysfunctions include oxidative stress, energy deficiency, programmed cell death, and calcium dysregulation. Mitochondria are a fundamental energy-generating structure of eukaryotic cells. During ATP synthesis via energy transduction, producing reactive oxygen species from free radicals can damage various molecules, leading to mitochondrial impairment. Parkinson’s disease, Alzheimer’s disease (AD), Huntington’s disease, and amyotrophic lateral sclerosis (ALS) are common chronic neurodegenerative disorders in older adults, usually linked with dysfunction in the mitochondrial electron transport chain complexes. In healthy cells characterized by unceasing division and fusion, the process of the biogenesis of mitochondria is tightly bound to the nuclear and mitochondrial DNA. In unhealthy cells, however, division (fission) leads to the fragmentation of the mitochondrial network following brain injury. AD is associated with cytochrome oxidase deficiency and deregulation of metabolic enzymes, observed in nonneural cells such as fibroblasts, platelets, and peripheral blood cells. Friedreich’s ataxia results from an expanded GAA repeat that disrupts the function of frataxin, leading to iron accumulation and oxidative damage. Familial ALS is linked to point mutations in superoxide dismutase, which may increase free radical production, exacerbating mitochondrial dysfunction. This review aims to explore the role of mitochondrial dysfunction in cellular metabolism and its implications for the progression of degenerative diseases. This article seeks to analyze how disruptions in mitochondrial function contribute to disease pathology, focusing on the mechanisms by which mitochondrial deficits impact metabolic processes across various degenerative conditions.