mitochondrial import inner membrane translocase subunit TIM8A; deafness dystonia protein 1; X-linked deafness dystonia protein (TIMM8A, DDP, DDP1, TIM8A)
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Function
- mitochondrial intermembrane chaperone
- participates in the import & insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane
- required for the transfer of beta-barrel precursors from the TOM complex to the sorting & assembly machinery (SAM complex) of the outer membrane
- acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation & guide them through the mitochondrial intermembrane space
- the TIMM8-TIMM13 complex mediates the import of proteins such as TIMM23, SLC25A12/ARALAR1 & SLC25A13/ARALAR2
- forms heterohexamer; composed of 3 copies of TIMM8A & 3 copies of TIMM13, named soluble 70 kD complex.
- the predominant TIMM9-TIMM10 70 kD complex mediates the import of much more proteins
- probably necessary for normal neurologic development
- associates with the TIM22 complex, whose core is composed of TIMM22
Structure
- the twin CX3C motif contains 4 conserved Cys that form 2 disulfide bonds in the mitochondrial intermembrane space
- during the transit of TIMM8A from cytoplasm into mitochondrion
- the Cys probably coordinate Zn+2, thereby preventing folding & allowing its transfer across mitochondrial outer membrane (putative)
- belongs to the small Tim family
Compartment
- mitochondrial inner membrane, intermembrane side (putative)
Expression
- expressed in fetal & adult brain > fetal lung, liver & kidney
- also expressed in heart, placenta, lung, liver, kidney, pancreas, skeletal muscle & heart
Pathology
- defects in TIMM8A are the cause of
- dsytonia deafness syndrome (Mohr-Tranebjaerg syndrome)
- Jensen syndrome