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How can mitochondrial dysfunction contribute to diseases affecting the brain and other organs?
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mitochondrion
Mitochondria (red) are found throughout the cytoplasm of almost all eukaryotic cells (cell nucleus is shown in blue; cytoskeleton is shown in yellow).
Mitochondrial dysfunction contributes to diseases affecting the brain and other organs primarily by disrupting the electron transport chain, which is the cell's primary energy-generating apparatus. When this system fails, it leads to several damaging consequences:12
- Energy Deficit: Impaired production of adenosine triphosphate (ATP) deprives high-energy tissues, such as the brain and muscles, of the fuel required for normal function.312
- Oxidative Stress: Dysfunction often causes the leakage of electrons, leading to the production of toxic reactive oxygen species (ROS). These free radicals damage cellular components, including mitochondrial DNA and proteins, further exacerbating organ failure.3142
- Cell Death: Damaged mitochondria may release apoptotic factors that trigger apoptosis (programmed cell death). Conversely, if this process is inhibited, it can contribute to the development of cancer.32
- Metabolic By-products: The buildup of unused metabolic intermediates can result in the accumulation of harmful substances like lactic acid.1
These mechanisms are implicated in various neurodegenerative conditions, including Alzheimer disease, Parkinson disease, and Huntington disease, as well as systemic issues like cardiomyopathy and diabetes.312