This review focuses on the role of mitochondria in brain physiology and pathology, emphasizing their multifaceted contributions to brain functions and the development of neurological diseases. Mitochondria are essential for energy production, redox regulation, and protein synthesis, and their dysfunctions are closely linked to various brain disorders. The review highlights the following key points: 1. **Mitochondrial Biology and Brain Physiology**: Mitochondria are crucial for brain function, providing energy through ATP production and maintaining redox balance. They are involved in calcium signaling, lipid metabolism, and the synthesis of neurotransmitters. 2. **Mitochondrial Energy Supply**: The brain's high metabolic demand is met by mitochondria, which generate ATP through oxidative phosphorylation. Abnormalities in mitochondrial energy metabolism are common in neurodegenerative diseases like Alzheimer's and Parkinson's. 3. **ROS Generation and Antioxidant Defense**: Mitochondria produce reactive oxygen species (ROS) during energy metabolism, which can cause oxidative stress. However, they also possess antioxidant enzymes and endogenous antioxidants to balance redox states. 4. **Independent Genome and Mutagenesis**: The mitochondrial DNA (mtDNA) is prone to mutations due to its proximity to OXPHOS sites and limited repair capacity, leading to neurological disturbances in diseases such as Parkinsonism and Alzheimer's. 5. **Membrane Dynamics and Quality Control**: Mitochondrial fusion and fission maintain functional mitochondria under stress, while mitophagy clears damaged mitochondria. These processes are critical for maintaining neuronal homeostasis. 6. **Cell Fate and Immunoregulation**: Mitochondria play a central role in cell death pathways, including apoptosis, necroptosis, and pyroptosis. They also regulate immune responses through mtDNA release and ROS production. 7. **Autophagy and Communication**: Autophagy, facilitated by mitochondria, is essential for removing protein aggregates and damaged organelles. Mitochondrial transfer between cells, such as neurons and astrocytes, is a promising therapeutic strategy. 8. **Neurological Diseases and Mitochondrial Dysfunctions**: Mitochondrial dysfunctions are prevalent in aging, neurodegeneration, psychiatric disorders, and brain injuries. These dysfunctions can lead to energy hypometabolism, oxidative stress, and protein aggregation. 9. **Therapeutic Approaches**: Mitochondrial-targeting therapeutics show great potential in treating brain diseases, including neurodegenerative disorders and psychiatric conditions. The review underscores the importance of understanding mitochondrial biology to develop effective treatments for neurological diseases.This review focuses on the role of mitochondria in brain physiology and pathology, emphasizing their multifaceted contributions to brain functions and the development of neurological diseases. Mitochondria are essential for energy production, redox regulation, and protein synthesis, and their dysfunctions are closely linked to various brain disorders. The review highlights the following key points: 1. **Mitochondrial Biology and Brain Physiology**: Mitochondria are crucial for brain function, providing energy through ATP production and maintaining redox balance. They are involved in calcium signaling, lipid metabolism, and the synthesis of neurotransmitters. 2. **Mitochondrial Energy Supply**: The brain's high metabolic demand is met by mitochondria, which generate ATP through oxidative phosphorylation. Abnormalities in mitochondrial energy metabolism are common in neurodegenerative diseases like Alzheimer's and Parkinson's. 3. **ROS Generation and Antioxidant Defense**: Mitochondria produce reactive oxygen species (ROS) during energy metabolism, which can cause oxidative stress. However, they also possess antioxidant enzymes and endogenous antioxidants to balance redox states. 4. **Independent Genome and Mutagenesis**: The mitochondrial DNA (mtDNA) is prone to mutations due to its proximity to OXPHOS sites and limited repair capacity, leading to neurological disturbances in diseases such as Parkinsonism and Alzheimer's. 5. **Membrane Dynamics and Quality Control**: Mitochondrial fusion and fission maintain functional mitochondria under stress, while mitophagy clears damaged mitochondria. These processes are critical for maintaining neuronal homeostasis. 6. **Cell Fate and Immunoregulation**: Mitochondria play a central role in cell death pathways, including apoptosis, necroptosis, and pyroptosis. They also regulate immune responses through mtDNA release and ROS production. 7. **Autophagy and Communication**: Autophagy, facilitated by mitochondria, is essential for removing protein aggregates and damaged organelles. Mitochondrial transfer between cells, such as neurons and astrocytes, is a promising therapeutic strategy. 8. **Neurological Diseases and Mitochondrial Dysfunctions**: Mitochondrial dysfunctions are prevalent in aging, neurodegeneration, psychiatric disorders, and brain injuries. These dysfunctions can lead to energy hypometabolism, oxidative stress, and protein aggregation. 9. **Therapeutic Approaches**: Mitochondrial-targeting therapeutics show great potential in treating brain diseases, including neurodegenerative disorders and psychiatric conditions. The review underscores the importance of understanding mitochondrial biology to develop effective treatments for neurological diseases.