MITOCHONDRIAL DYSFUNCTION IN DISEASE: PATHOGENIC MECHANISMS AND NOVEL THERAPIES

Mitochondria serve as vital cellular components with functions extending far beyond ATP generation, encompassing calcium homeostasis, oxidative balance, and programmed cell death regulation. Their malfunction contributes to a wide spectrum of disorders spanning neurological (Alzheimer's, Parkinson's), metabolic (diabetes), cardiac, liver, and cancerous conditions. Shared disease mechanisms include disrupted energy production, oxidative stress, impaired organelle dynamics, and persistent mtDNA damage. In neurological degeneration, mitochondrial impairment initiates and worsens protein aggregation pathologies, whereas in metabolic diseases it promotes insulin insensitivity and fat deposition. Malignant cells hijack mitochondrial adaptability to support growth and treatment evasion. Current therapies primarily address symptoms, though innovative approaches show potential: mitochondria-specific antioxidants (MitoQ), dynamics regulators (DRP1 blockers), mitophagy stimulators, and genetic interventions. Emerging techniques include mitochondrial transfer and nanoparticle-based delivery systems. Non-pharmacological approaches like physical activity positively influence mitochondrial performance. Critical obstacles involve enhancing drug targeting precision, reducing unintended effects, and improving clinical applicability. Future priorities should emphasize establishing robust biomarkers, creating standardized disease databases, and advancing tailored treatment protocols. Deciphering mitochondrial disease mechanisms holds revolutionary promise for managing chronic illnesses, connecting basic science with therapeutic implementation.