title: Cardiolipin and mitochondrial phosphatidylethanolamine have overlapping functions in mitochondrial fusion in Saccharomyces cerevisiae.
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.
authors.affiliation: Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202 and.
authors.forename: Amit S
authors.initials: AS
authors.lastname: Joshi
authors.affiliation: Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202 and.
authors.forename: Morgan N
authors.initials: MN
authors.lastname: Thompson
authors.affiliation: Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202 and.
authors.forename: Naomi
authors.initials: N
authors.lastname: Fei
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan 48201.
authors.forename: Maik
authors.initials: M
authors.lastname: Hüttemann
authors.affiliation: Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202 and. Electronic address: mlgreen@sun.science.wayne.edu.
authors.forename: Miriam L
authors.initials: ML
authors.lastname: Greenberg
mesh_terms: D002262:Carboxy-Lyases / Q000235:genetics / Q000378:metabolism; D002308:Cardiolipins / Q000096:biosynthesis* / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D008561:Membrane Fusion / Q000502:physiology*; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D010714:Phosphatidylethanolamines / Q000096:biosynthesis* / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics / Q000378:metabolism
chemical_list: D002308:Cardiolipins; C082883:MGM1 protein, S cerevisiae; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010714:Phosphatidylethanolamines; D029701:Saccharomyces cerevisiae Proteins; C483858:phosphatidylethanolamine; D017855:Transferases (Other Substituted Phosphate Groups); C100091:cardiolipin synthetase; D019204:GTP-Binding Proteins; D002262:Carboxy-Lyases; C022353:phosphatidylserine decarboxylase