The article reviews the impact of *MT-ND1* gene mutations on disease progression, focusing on their effects on various diseases and the possible mechanisms involved. *MT-ND1*, a core subunit of mitochondrial respiratory chain complex I, plays a crucial role in the assembly and function of complex I. Mutations in *MT-ND1* can affect the early assembly of complex I, the ubiquinone binding domain, and the proton channel, leading to impaired oxidative phosphorylation and various diseases. Key findings include: 1. **Assembly of Complex I**: Mutations in *MT-ND1* can disrupt the formation of the 400 kDa subcomplex required for the early assembly of complex I, affecting its stability and activity. 2. **Ubiquinone Binding and Proton Channel**: *MT-ND1* is involved in the ubiquinone binding domain and proton channel of complex I, which are essential for energy conversion. Mutations can alter the structure and function of these domains, leading to reduced ATP production and increased reactive oxygen species (ROS) production. 3. **Disease Association**: - **Leber Hereditary Optic Neuropathy (LHON)**: Mutations in *MT-ND1* are a major cause of LHON, leading to rapid visual loss due to mitochondrial dysfunction and increased ROS production. - **Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)**: *MT-ND1* mutations are associated with MELAS, causing encephalomyopathy and sensorineural hearing loss. - **Type 2 Diabetes (T2D)**: Mutations in *MT-ND1* can contribute to T2D by affecting mitochondrial ATP production and ROS levels. - **Other Diseases**: *MT-ND1* mutations are also linked to neurological disorders, cardiovascular diseases, hearing loss, and cancer. 4. **Diagnosis and Treatment**: - **Diagnosis**: *MT-ND1* mutations can be detected in various tissues and fluids, aiding in disease diagnosis. - **Treatment**: Ectopic expression of *MT-ND1* or regulatory strategies can improve disease phenotypes, such as in LHON and T2D. The article highlights the need for further research to understand the detailed mechanisms of *MT-ND1* mutations and their impact on diseases, as well as the potential for targeted therapies based on *MT-ND1* expression and mutation levels.The article reviews the impact of *MT-ND1* gene mutations on disease progression, focusing on their effects on various diseases and the possible mechanisms involved. *MT-ND1*, a core subunit of mitochondrial respiratory chain complex I, plays a crucial role in the assembly and function of complex I. Mutations in *MT-ND1* can affect the early assembly of complex I, the ubiquinone binding domain, and the proton channel, leading to impaired oxidative phosphorylation and various diseases. Key findings include: 1. **Assembly of Complex I**: Mutations in *MT-ND1* can disrupt the formation of the 400 kDa subcomplex required for the early assembly of complex I, affecting its stability and activity. 2. **Ubiquinone Binding and Proton Channel**: *MT-ND1* is involved in the ubiquinone binding domain and proton channel of complex I, which are essential for energy conversion. Mutations can alter the structure and function of these domains, leading to reduced ATP production and increased reactive oxygen species (ROS) production. 3. **Disease Association**: - **Leber Hereditary Optic Neuropathy (LHON)**: Mutations in *MT-ND1* are a major cause of LHON, leading to rapid visual loss due to mitochondrial dysfunction and increased ROS production. - **Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)**: *MT-ND1* mutations are associated with MELAS, causing encephalomyopathy and sensorineural hearing loss. - **Type 2 Diabetes (T2D)**: Mutations in *MT-ND1* can contribute to T2D by affecting mitochondrial ATP production and ROS levels. - **Other Diseases**: *MT-ND1* mutations are also linked to neurological disorders, cardiovascular diseases, hearing loss, and cancer. 4. **Diagnosis and Treatment**: - **Diagnosis**: *MT-ND1* mutations can be detected in various tissues and fluids, aiding in disease diagnosis. - **Treatment**: Ectopic expression of *MT-ND1* or regulatory strategies can improve disease phenotypes, such as in LHON and T2D. The article highlights the need for further research to understand the detailed mechanisms of *MT-ND1* mutations and their impact on diseases, as well as the potential for targeted therapies based on *MT-ND1* expression and mutation levels.