After biosynthesis, an evolutionarily conserved acyl chain remodeling process generates a final highly homogeneous and yet tissue-specific molecular form of the mitochondrial
lipid cardiolipin. Hence,
cardiolipin molecules in different organisms, and even different tissues within the same organism, contain a distinct collection of attached acyl chains. This observation is the basis for the widely accepted paradigm that the acyl chain composition of
cardiolipin is matched to the unique mitochondrial demands of a tissue. For this hypothesis to be correct,
cardiolipin molecules with different acyl chain compositions should have distinct functional capacities, and
cardiolipin that has been remodeled should promote
cardiolipin-dependent mitochondrial processes better than its unremodeled form. However, functional disparities between different molecular forms of
cardiolipin have never been established. Here, we interrogate this simple but crucial prediction utilizing the best available model to do so, Saccharomyces cerevisiae. Specifically, we compare the ability of unremodeled and remodeled
cardiolipin, which differ markedly in their acyl chain composition, to support mitochondrial activities known to require
cardiolipin. Surprisingly, defined changes in the acyl chain composition of
cardiolipin do not alter either mitochondrial morphology or oxidative phosphorylation. Importantly, preventing
cardiolipin remodeling initiation in yeast lacking TAZ1, an ortholog of the causative gene in
Barth syndrome, ameliorates
mitochondrial dysfunction. Thus, our data do not support the prevailing hypothesis that unremodeled
cardiolipin is functionally distinct from remodeled
cardiolipin, at least for the functions examined, suggesting alternative physiological roles for this conserved pathway.