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Cardiolipin deficiency causes triacylglycerol accumulation in Saccharomyces cerevisiae

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Abstract

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.

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Acknowledgements

This work was supported by the Council of Scientific and Industrial Research (CSIR), New Delhi, under the 12th 5-year plan project LIPIC. P.K.Y. was supported by a fellowship from CSIR, New Delhi. The corresponding author is a recipient of the JC Bose National Fellowship. We are thankful to Prof. Vasanthi Nachiappan of the Department of Biochemistry at Bharathidasan University in India for providing the pUG34 vector. We are grateful to the Department of Biochemistry of the Indian Institute of Science in Bangalore for extending their facility for the radioactive study.

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Authors and Affiliations

  1. Lipidomic Centre, Department of Lipid Science, CSIR-Central Food Technological Research Institute (CFTRI), Council of Scientific and Industrial Research, Mysore, Karnataka, 570020, India

    Pradeep Kumar Yadav & Ram Rajasekharan

  2. Academy of Scientific & Innovative Research, CSIR-CFTRI, Mysore, India

    Pradeep Kumar Yadav & Ram Rajasekharan

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  1. Pradeep Kumar Yadav
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  2. Ram Rajasekharan
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RR conceived and initiated the project. RR and PKY designed the experiments. PKY executed the experiments and analyzed the data. PKY and RR discussed the data and wrote the paper.

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Correspondence to Ram Rajasekharan.

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Yadav, P.K., Rajasekharan, R. Cardiolipin deficiency causes triacylglycerol accumulation in Saccharomyces cerevisiae . Mol Cell Biochem 434, 89–103 (2017). https://doi.org/10.1007/s11010-017-3039-4

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