Cardiolipin deficiency causes triacylglycerol accumulation in Saccharomyces cerevisiae.

In yeast, the synthesis of cardiolipin (CL) and
phosphatidylethanolamine (PE) occurs mainly in mitochondria.
CL and PE have overlapping functions, and they
are required for mitochondrial function. PE is physiologically
linked with triacylglycerol (TAG) metabolism in
Saccharomyces cerevisiae, involving an acyl-CoA-independent
pathway through the phospholipid:diacylglycerol
acyltransferase activity of the Lro1 protein. There is no
report on the physiological link between CL and TAG
metabolism. Here we report a metabolic link between CL
and TAG accumulation in the S. cerevisiae. Our data
indicated that CL deficiency causes TAG accumulation,
involving an acyl-CoA-dependent pathway through the
diacylglycerol acyltransferase activity of the Dga1 protein
with no changes in the TAG molecular species. The DGA1
gene deletion from the CL-deficient strains reduced the
TAG levels. Data from in vitro and in vivo analyses
showed that CL did not affect the enzymatic activity of
Dga1. Our data also showed that CL deficiency leads to the
up-regulation of acetyl-CoA synthetase genes (ACS1 and
ACS2) of the cytosolic pyruvate dehydrogenase bypass
pathway. This study establishes a physiological link
between CL and TAG metabolism in S. cerevisiae.