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Vol. 19, Issue 12, 5047-5058, December 2008

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Cardiolipin Mediates Cross-Talk between Mitochondria and the Vacuole

Shuliang Chen^*, Maureen Tarsio, Patricia M. Kane, and Miriam L. Greenberg^*

*Department of Biological Sciences, Wayne State University, Detroit, MI 48202; and Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13201

Submitted May 15, 2008; Revised August 22, 2008; Accepted September 8, 2008
Monitoring Editor: Thomas D. Fox

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 crd1 mutant exhibits severe vacuolar defects, including swollen vacuole morphology and loss of vacuolar acidification, at 37°C. Moreover, vacuoles from crd1 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 crd1, strongly suggesting that the temperature sensitivity of crd1 is a consequence of the vacuolar defects. Our results demonstrate the existence of a novel mitochondria-vacuole signaling pathway mediated by CL synthesis.

Address correspondence to: Miriam L. Greenberg (mlgreen{at}sun.science.wayne.edu).

Abbreviations used: ACMA, 9-amino-6-chloro-2-methoxyacridine; CL, cardiolipin; PG, phosphatidylglycerol; WT, wild type.

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