Barth syndrome mutations that cause tafazzin complex lability

Steven M. Claypool, Kevin Whited, Santi Srijumnong, Xianlin Han, Carla M. Koehler

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Deficits in mitochondrial function result in many human diseases. The X-linked disease Barth syndrome (BTHS) is caused by mutations in the tafazzin gene TAZ1. Its product, Taz1p, participates in the metabolism of cardiolipin, the signature phospholipid of mitochondria. In this paper, a yeast BTHS mutant tafazzin panel is established, and 18 of the 21 tested BTHS missense mutations cannot functionally replace endogenous tafazzin. Four BTHS mutant tafazzins expressed at low levels are degraded by the intermembrane space AAA (i-AAA) protease, suggesting misfolding of the mutant polypeptides. Paradoxically, each of these mutant tafazzins assembles in normal protein complexes. Furthermore, in the absence of the i-AAA protease, increased expression and assembly of two of the BTHS mutants improve their function. However, the BTHS mutant complexes are extremely unstable and accumulate as insoluble aggregates when disassembled in the absence of the i-AAA protease. Thus, the loss of function for these BTHS mutants results from the inherent instability of the mutant tafazzin complexes.

Original languageEnglish (US)
Pages (from-to)447-462
Number of pages16
JournalJournal of Cell Biology
Issue number3
StatePublished - Feb 7 2011
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology


Dive into the research topics of 'Barth syndrome mutations that cause tafazzin complex lability'. Together they form a unique fingerprint.

Cite this