Role of the deafness dystonia peptide 1 (DDP1) in import of human Tim23 into the inner membrane of mitochondria.
Tim8 and Tim13 of yeast belong to a family of evolutionary conserved zinc finger proteins that are organized in hetero-oligomeric complexes in the mitochondrial intermembrane space. Mutations in DDP1 (deafness dystonia peptide 1), the human homolog of Tim8, are associated with the Mohr-Tranebjaerg syndrome, a progressive neurodegenerative disorder. We show that DDP1 acts with human Tim13 in a complex in the intermembrane space. The DDP1.hTim13 complex is in direct contact with translocation intermediates of human Tim23 in mammalian mitochondria. The human DDP1.hTim13 complex complements the function of the TIM8.13 complex in yeast and facilitates import of yeast and human Tim23. Thus, the pathomechanism underlying the Mohr-Tranebjaerg syndrome may involve an impaired biogenesis of the human TIM23 complex causing severe pleiotropic mitochondrial dysfunction.
Rothbauer
U
U
Institut für Klinische Chemie, Molekulare Diagnostik und Mitochondriale Genetik, Akademisches Lehrkrankenhaus München-Schwabing, Koelner Platz 1, München 80804, Germany.
Hofmann
S
S
Mühlenbein
N
N
Paschen
S A
SA
Gerbitz
K D
KD
Neupert
W
W
Brunner
M
M
Bauer
M F
MF
D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D011108:Polymers; D029701:Saccharomyces cerevisiae Proteins
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D011108:Polymers; D029701:Saccharomyces cerevisiae Proteins; C403093:TIM13 protein, S cerevisiae; C485737:TIMM13 protein, human; C438387:TIMM23 protein, human; C118122:TIMM8A protein, human; C017800:zinc-binding protein