GxxxG motifs hold the TIM23 complex together

Keren Demishtein-Zohary, Milit Marom, Walter Neupert, Dejana Mokranjac*, Abdussalam Azem

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Approximately 99% of the mitochondrial proteome is nucleus-encoded, synthesized in the cytosol, and subsequently imported into and sorted to the correct compartment in the organelle. The translocase of the inner mitochondrial membrane 23 (TIM23) complex is the major protein translocase of the inner membrane, and is responsible for translocation of proteins across the inner membrane and their insertion into the inner membrane. Tim23 is the central component of the complex that forms the import channel. A high-resolution structure of the import channel is still missing, and structural elements important for its function are unknown. In the present study, we analyzed the importance of the highly abundant GxxxG motifs in the transmembrane segments of Tim23 for the structural integrity of the TIM23 complex. Of 10 glycines present in the GxxxG motifs in the first, second and third transmembrane segments of Tim23, mutations of three of them in transmembrane segments 1 and 2 resulted in a lethal phenotype, and mutations of three others in a temperature-sensitive phenotype. The remaining four caused no obvious growth phenotype. Importantly, none of the mutations impaired the import and membrane integration of Tim23 precursor into mitochondria. However, the severity of growth impairment correlated with the destabilization of the TIM23 complex. We conclude that the GxxxG motifs found in the first and second transmembrane segments of Tim23 are necessary for the structural integrity of the TIM23 complex. We studied the role of GxxxG motifs, which exist in three out of the four trans-membrane helices of Tim23. Out of ten glycines in the motifs, mutations of six resulted in impaired growth phenotypes. The severity of the growth impairment correlated with the destabilization of the TIM23 complex. We conclude that these motifs are critical for the integrity of the complex.

Original languageEnglish
Pages (from-to)2178-2186
Number of pages9
JournalFEBS Journal
Volume282
Issue number11
DOIs
StatePublished - 1 Jun 2015

Keywords

  • Tim17
  • Tim23
  • Tim44
  • import channel
  • mitochondrial protein import

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