The mitochondrial quality control protein Yme1 is necessary to prevent defective mitophagy in a yeast model of Barth Syndrome [Lipids]

February 16th, 2015 by Gaspard, G. J., McMaster, C. R.

The Saccharomyces cerevisiae TAZ1 gene is an orthologue of human TAZ, both encode the protein tafazzin. Tafazzin is a transacylase that transfers acyl chains with unsaturated fatty acids from phospholipids to monolysocardiolipin (MLCL) to generate CL with unsaturated fatty acids. Mutations in human TAZ cause Barth Syndrome (BTHS), a fatal childhood cardiomyopathy biochemically characterized by reduced CL mass and increased MLCL levels. To uncover cellular processes that require tafazzin to maintain cell health, we performed a synthetic genetic array (SGA) screen using taz1Δ yeast cells to identify genes whose deletion aggravated its fitness. The SGA screen uncovered several mitochondrial cellular processes that require tafazzin. Focusing on the i-AAA protease Yme1, a mitochondrial quality control protein that degrades misfolded proteins, we determined that in cells lacking both Yme1 and Taz1 function there were substantive mitochondrial ultrastructural defects, ineffective superoxide scavenging, and a severe defect in mitophagy. We identify an important role for the mitochondrial protease Yme1 in the ability of cells that lack tafazzin function to maintain mitochondrial structural integrity, mitochondrial quality control, and undergo mitophagy.