MITOCHONDRIAL DYSFUNCTION IN DISEASE: PATHOGENIC MECHANISMS AND NOVEL THERAPIES

Michał Wycik; Hubert Chmielewski; Julia Komar; Artur Wądołowski; Gabriela Kondratiuk; Ada Kondrat; Michał Szczupak; Paweł Mierzejewski; Justyna Werno; Zuzanna Twarowska

doi:10.31435/ijitss.4(48).2025.4424

Authors

Michał Wycik University Clinical Hospital in Białystok, Białystok, Poland https://orcid.org/0009-0007-3052-9924
Hubert Chmielewski Medical University of Białystok, Białystok, Poland https://orcid.org/0009-0000-5697-518X
Julia Komar Medical University of Białystok, Białystok, Poland https://orcid.org/0009-0008-9104-7934
Artur Wądołowski University Clinical Hospital in Białystok, Białystok, Poland https://orcid.org/0009-0006-0261-581X
Gabriela Kondratiuk Medical University of Białystok, Białystok, Poland https://orcid.org/0009-0009-4181-731X
Ada Kondrat University Clinical Hospital in Białystok, Białystok, Poland https://orcid.org/0009-0008-0823-0544
Michał Szczupak University Clinical Hospital in Białystok, Białystok, Poland https://orcid.org/0009-0005-5112-6978
Paweł Mierzejewski University Clinical Hospital in Białystok, Białystok, Poland https://orcid.org/0009-0009-2004-9972
Justyna Werno University of Zielona Góra, Zielona Góra, Poland https://orcid.org/0009-0002-9681-3323
Zuzanna Twarowska University Clinical Hospital in Białystok, Białystok, Poland https://orcid.org/0009-0006-8662-099X

DOI:

https://doi.org/10.31435/ijitss.4(48).2025.4424

Keywords:

Mitochondria, Oxidative Stress, Mitochondrial Dynamics, Neurodegenerative Diseases, Metabolic Disorders, Cancer Therapy, Mitochondrial-Targeted Treatments, Personalized Medicine

Abstract

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.

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