Ptpmt1-KO Mouse

PTPMT1, a mitochondrial tyrosine phosphatase, is essential for de novo cardiolipin biosynthesis in mitochondria. Cardiolipin, a key phospholipid in the inner mitochondrial membrane, is involved in multiple mitochondrial functions, thus highlighting PTPMT1's significance in maintaining mitochondrial integrity and function. Zebrafish and fly models have been used to study its functions [1,4].

Six individuals from three families with biallelic PTPMT1 variants presented a neonatal/infantile onset neurological and neurodevelopmental syndrome. Patient-derived cells and a ptpmt1 knockout zebrafish model showed abnormal mitochondrial structure and function, decreased cardiolipin levels, and OXPHOS deficiency, indicating that PTPMT1 loss-of-function causes a new autosomal recessive primary mitochondrial disease due to impaired cardiolipin metabolism [1]. In pancreatic cancer cells, PTPMT1 silencing reduced cell viability, caused mitochondrial damage, and impaired mitochondrial function, suggesting it may modulate mitochondrial function via the SLC25A6-NDUFS2 axis [3]. In irradiated cardiomyocytes, γ-ray irradiation decreased PTPMT1 expression, increased oxidative stress, and induced mitochondrial dysfunction and necroptosis, while overexpression of PTPMT1 alleviated these effects [2].

In conclusion, PTPMT1 is crucial for maintaining normal mitochondrial function, especially in cardiolipin metabolism. Studies using gene-knockout models in zebrafish and in functional knockdown in mammalian cells have revealed its role in various disease-related processes such as neurodevelopmental syndromes, pancreatic cancer, and radiation-induced heart disease. These findings highlight the importance of PTPMT1 in understanding the mechanisms underlying these diseases and potentially developing new therapeutic strategies.