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 TET(OFF) 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.
Highlights
Cells lacking both cardiolipin and mitochondrial phosphatidylethanolamine are inviable, suggesting that these lipids have overlapping functions
We demonstrate that crd1⌬psd1⌬ cells lacking both CL and mitochondrial PE have fragmented mitochondria due to a defect in mitochondrial fusion
In addition to this defect, we show that crd1⌬psd1⌬ cells exhibit loss of mitochondrial DNA (mtDNA), decreased membrane potential, and reduced steady state levels of short and long isoforms of Mgm1p, a mitochondrial inner membrane protein essential for fusion
Summary
Cells lacking both cardiolipin and mitochondrial phosphatidylethanolamine are inviable, suggesting that these lipids have overlapping functions. 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. 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. We hypothesized that the mitochondrial phospholipids CL and PE have overlapping functions in mitochondrial fusion in vivo Consistent with this hypothesis, we demonstrate that cells lacking both CL and mitochondrial PE have reduced levels of both Mgm1p isoforms and exhibit.
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