The calcium-binding aspartate/glutamate carriers, citrin and aralar1, are new substrates for the DDP1/TIMM8a-TIMM13 complex
| Autor: | Carla M. Koehler, Lisbeth Tranebjærg, Peter J. Hynds, Renee Varga, Karin Roesch |
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| Rok vydání: | 2004 |
| Předmět: |
Mitochondrial intermembrane space
Translocase of the outer membrane Organic Anion Transporters Saccharomyces cerevisiae Mitochondrion Biology Deafness Mitochondrial Membrane Transport Proteins Cell Line Mitochondrial Proteins Mice Purkinje Cells Mitochondrial Precursor Protein Import Complex Proteins Genetics Animals Humans Immunoprecipitation Inner mitochondrial membrane Molecular Biology Genetics (clinical) Calcium-Binding Proteins Membrane Transport Proteins General Medicine Intracellular Membranes Syndrome Mitochondrial carrier Mitochondria Dystonia Biochemistry Mitochondrial matrix Translocase of the inner membrane Heredodegenerative Disorders Nervous System ATP–ADP translocase |
| Zdroj: | Human molecular genetics. 13(18) |
| ISSN: | 0964-6906 |
| Popis: | The biogenesis of the mitochondrial inner membrane is dependent on two distinct 70 kDa protein complexes. TlMM8a partners with TIMM13 in the mitochondrial intermembrane space to form a 70 kDa complex and facilitates the import of the inner membrane substrate TIMM23. We have identified a new class of substrates, citrin and aralarl, which are Ca 2+ -binding aspartate/glutamate carriers (AGCs) of the mitochondrial inner membrane, using cross-linking and immunoprecipitation assays in isolated mitochondria. The AGCs function in the aspartate-malate NADH shuttle that moves reducing equivalents from the cytosol to the mitochondrial matrix. Mohr-Tranebjaerg syndrome (MTSIDFN-1, deafnessldystonia syndrome) results from a mutation in deafness/dystonia protein 1/translocase of mitochondrial inner membrane 8a (DDP1/TIMM8a) and loss of the 70 kDa complex. A lymphoblast cell line derived from an MTS patient had decreased NADH levels and defects in mitochondrial protein import. Protein expression studies indicate that DDP1 and TIMM13 show non-uniform expression in mammals, and expression is prominent in the large neurons in the brain, which is in agreement with the expression pattern of aralar1. Thus, insufficient NADH shuttling, linked with changes in Ca 2+ concentration, in sensitive cells of the central nervous system might contribute to the pathologic process associated with MTS. |
| Databáze: | OpenAIRE |
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