title: Cardiolipin mediates cross-talk between mitochondria and the vacuole.
abstract: Cardiolipin (CL) is an anionic phospholipid with a dimeric structure predominantly localized in the mitochondrial inner membrane, where it is closely associated with mitochondrial function, biogenesis, and genome stability (Daum, 1985; Janitor and Subik, 1993; Jiang et al., 2000; Schlame et al., 2000; Zhong et al., 2004). Previous studies have shown that yeast mutant cells lacking CL due to a disruption in CRD1, the structural gene encoding CL synthase, exhibit defective colony formation at elevated temperature even on glucose medium (Jiang et al., 1999; Zhong et al., 2004), suggesting a role for CL in cellular processes apart from mitochondrial bioenergetics. In the current study, we present evidence that the crd1Delta mutant exhibits severe vacuolar defects, including swollen vacuole morphology and loss of vacuolar acidification, at 37 degrees C. Moreover, vacuoles from crd1Delta show decreased vacuolar H(+)-ATPase activity and proton pumping, which may contribute to loss of vacuolar acidification. Deletion mutants in RTG2 and NHX1, which mediate vacuolar pH and ion homeostasis, rescue the defective colony formation phenotype of crd1Delta, strongly suggesting that the temperature sensitivity of crd1Delta is a consequence of the vacuolar defects. Our results demonstrate the existence of a novel mitochondria-vacuole signaling pathway mediated by CL synthesis.
authors.affiliation: Department of Biological Sciences, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Shuliang
authors.initials: S
authors.lastname: Chen
authors.forename: Maureen
authors.initials: M
authors.lastname: Tarsio
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Kane
authors.forename: Miriam L
authors.initials: ML
authors.lastname: Greenberg
mesh_terms: D002308:Cardiolipins / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D048430:Cell Shape; D006706:Homeostasis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism; D013696:Temperature; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D002308:Cardiolipins; D027682:Cation Transport Proteins; D047908:Intracellular Signaling Peptides and Proteins; C492183:NHX1 protein, S cerevisiae; C079379:RTG2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D017923:Sodium-Hydrogen Exchangers; D025262:Vacuolar Proton-Translocating ATPases
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