TIMM8A

TIMM8A is a human gene encoding a protein also known as deafness dystonia peptide 1 (DDP1). It is a member of the small TIM family of proteins. These proteins are involved in the import and assembly of inner mitochondrial membrane proteins. TIMM8A is located on the X chromosome.

Function:

The protein encoded by the TIMM8A gene functions as a chaperone in the intermembrane space of mitochondria. It is involved in the translocation of hydrophobic proteins from the cytosol to the mitochondrial inner membrane. It forms a complex with TIMM13, another small TIM protein, and this complex is crucial for the import and assembly of certain inner mitochondrial membrane proteins. These imported proteins are essential for mitochondrial function, including oxidative phosphorylation and ATP production.

Clinical Significance:

Mutations in the TIMM8A gene are associated with Mohr-Tranebjaerg syndrome (also known as deafness-dystonia peptide 1 syndrome, or DDP1), an X-linked recessive neurodegenerative disorder. This syndrome is characterized by sensorineural deafness, dystonia, optic atrophy, and intellectual disability. The mutations in TIMM8A disrupt the proper folding or function of the protein, leading to impaired mitochondrial protein import and subsequent mitochondrial dysfunction. This dysfunction particularly affects the central nervous system and auditory system, causing the neurological and auditory symptoms observed in Mohr-Tranebjaerg syndrome.

Interactions:

TIMM8A is known to interact with TIMM13, forming a heterohexameric complex. This complex is important for its chaperone function and its ability to interact with other mitochondrial import machinery.