Logo image
Back
Cardiolipin and Mitochondrial Phosphatidylethanolamine Have Overlapping Functions in Mitochondrial Fusion in Saccharomyces cerevisiae
Journal article   Open access   Peer reviewed

Cardiolipin and Mitochondrial Phosphatidylethanolamine Have Overlapping Functions in Mitochondrial Fusion in Saccharomyces cerevisiae

Amit S. Joshi, Morgan N. Thompson, Naomi Fei, Maik Hüttemann and Miriam L. Greenberg
The Journal of biological chemistry, Vol.287(21), pp.17589-17597
05/18/2012
DOI: 10.1074/jbc.M111.330167
PMCID: PMC3366806
PMID: 22433850
url
https://doi.org/10.1074/jbc.M111.330167View
Published (Version of record) Open Access

Abstract

The two non-bilayer forming mitochondrial phospholipids cardiolipin (CL) and phosphatidylethanolamine (PE) play crucial roles in maintaining mitochondrial morphology. We have shown previously that CL and PE have overlapping functions, and the loss of both is synthetically lethal. Because the lack of CL does not lead to defects in the mitochondrial network in Saccharomyces cerevisiae, we hypothesized that PE may compensate for CL in the maintenance of mitochondrial tubular morphology and fusion. To test this hypothesis, we constructed a conditional mutant crd1Δpsd1Δ containing null alleles of CRD1 (CL synthase) and PSD1 (mitochondrial phosphatidylserine decarboxylase), in which the wild type CRD1 gene is expressed on a plasmid under control of the TETOFF promoter. In the presence of tetracycline, the mutant exhibited highly fragmented mitochondria, loss of mitochondrial DNA, and reduced membrane potential, characteristic of fusion mutants. Deletion of DNM1, required for mitochondrial fission, restored the tubular mitochondrial morphology. Loss of CL and mitochondrial PE led to reduced levels of small and large isoforms of the fusion protein Mgm1p, possibly accounting for the fusion defect. Taken together, these data demonstrate for the first time in vivo that CL and mitochondrial PE are required to maintain tubular mitochondrial morphology and have overlapping functions in mitochondrial fusion. Cells lacking both cardiolipin and mitochondrial phosphatidylethanolamine are inviable, suggesting that these lipids have overlapping functions. The loss of both lipids leads to decreased mitochondrial fusion and fragmented mitochondria. One overlapping function of these lipids is in mitochondrial fusion. Decreased mitochondrial fusion may partly explain the variation in clinical presentation observed in Barth syndrome.
 Barth Syndrome Cardiolipin Membrane Lipids Mitochondria Mitochondrial Fusion Phosphatidylethanolamine Yeast

Details

Metrics

17 Record Views
160 Times Cited - Web of Science
Logo image