The Role of Mitochondrial Dysfunction in Neurodegenerative and Liver Diseases

Mitochondrial dysfunction is a key pathogenic mechanism in liver disease as in neuro degenerative diseases. In parkinsonian disorders (e.g. “Parkinson disease (PD), Alzheimer disease (AD) and ALS”), neuronal-specific energy- homeostasis and synaptic activity is impaired due to malfunctioning oxidative phosphorilation (OXPHOS) and ATP synthesis. The overproduction of “reactive oxygen species (ROS)” initiates oxidative stress, whereas the perturbed dynamics of mitochondria with disproportioned fission and fusion, incomplete trafficking, and reduced mitophagy deteriorate the mitochondrial health even further. Reduced expression of key regulators of “mitochondrial biogenesis” and metabolism, “such as PGC-1α and Tfam”, exacerbates these deficits, contributing to neuronal dysfunction, synaptic loss, and progressive neurodegeneration. In liver disorders such as “non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH)”, alcohol liver disease, and cirrhosis- the disruption of mitochondrial performance is characterized by poor fatty β-oxidation and OXPHOS, which leads to the shortage of energy and excessive storage of lipids. Elevated mitochondrial ROS generation promotes hepatocyte injury, inflammation, and fibrosis, while defective mitophagy and mitochondrial quality control accelerate disease progression from simple steatosis to advanced liver pathology. Mitochondrial DNA (mtDNA) damage and impaired expression of electron transport chain (ETC) components further worsen mitochondrial performance.