Functional Importance of Mitochondrial Cardiolipin in Yeast Cytochrome c Oxidase Activity

Trivedi, A.; Wearring, Andrew V.; Kohlwein, Sepp-Dieter; Paltauf, Fritz; Tustanoff, E. Reno

doi:10.1007/978-1-4899-2551-0_9

Integration of Mitochondrial Function 1988

DOI: 10.1007/978-1-4899-2551-0_9

|View full text |Cite

Functional Importance of Mitochondrial Cardiolipin in Yeast Cytochrome c Oxidase Activity

A. Trivedi

Andrew V. Wearring

Sepp-Dieter Kohlwein

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

1988

2000

Publication Types

Select...

Article8

Relationship

Self Cite0

Independent8

Authors

Journals

Cited by 12 publications

(8 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is associated with the major proteins of oxidative phosphorylation, including complex V (ATP synthase), respiratory complexes I, III, and IV, as well as the carrier proteins for phosphate and adenine nucleotides (12)(13)(14)(15)(16)(17). Trivedi et al (18) showed that a temperature-sensitive yeast mutant that had reduced CL at the elevated temperature had a concomitant decrease in cytochrome oxidase activity. In vitro experiments suggest that mitochondrial inner membrane integrity may depend specifically on CL, because enzymatic digestion of CL, but not PE or PC, correlates with the disruption of structure (19).…”

mentioning

confidence: 99%

Absence of Cardiolipin in the crd1 Null Mutant Results in Decreased Mitochondrial Membrane Potential and Reduced Mitochondrial Function

Jiang¹,

Ryan²,

Schlame³

et al. 2000

Journal of Biological Chemistry

370

386

View full text Add to dashboard Cite

Cardiolipin (CL) is a unique phospholipid which is present throughout the eukaryotic kingdom and is localized in mitochondrial membranes. Saccharomyces cerevisiae cells containing a disruption of CRD1, the structural gene encoding CL synthase, have no CL in mitochondrial membranes. To elucidate the physiological role of CL, we compared mitochondrial functions in the crd1⌬ mutant and isogenic wild type. The crd1⌬ mutant loses viability at elevated temperature, and prolonged culture at 37°C leads to loss of the mitochondrial genome. Mutant membranes have increased phosphatidylglycerol (PG) when grown in a nonfermentable carbon source but have almost no detectable PG in medium containing glucose. In glucose-grown cells, maximum respiratory rate, ATPase and cytochrome oxidase activities, and protein import are deficient in the mutant. The ADP/ATP carrier is defective even during growth in a nonfermentable carbon source. The mitochondrial membrane potential is decreased in mutant cells. The decrease is more pronounced in glucose-grown cells, which lack PG, but is also apparent in membranes containing PG (i.e. in nonfermentable carbon sources). We propose that CL is required for maintaining the mitochondrial membrane potential and that reduced membrane potential in the absence of CL leads to defects in protein import and other mitochondrial functions.1 is a structurally unique phospholipid that carries four acyl groups and two negative charges. It is thus highly hydrophobic and acidic. The biosynthesis of CL occurs in three enzymatic steps (1-3). Phosphatidylglycerolphosphate (PGP) synthase catalyzes the formation of PGP from phosphatidyl-CMP (CDP-diacylglycerol; CDP-DG) and glycerol 3-phosphate. PGP is then dephosphorylated to phosphatidylglycerol (PG) by PGP phosphatase. Eukaryotes and bacteria utilize different reactions to convert PG to CL. In prokaryotes, CL synthase catalyzes a phosphatidyl transfer between two PG molecules (4). This is a near-equilibrium (transesterification) reaction that is mainly controlled by substrate availability. In contrast, eukaryotic CL synthase catalyzes a phosphatidyl transfer from CDP-DG to PG (5-7). This is an irreversible reaction that involves cleavage of a high energy anhydride bond. This reaction can take place in the presence of low substrate concentration and is mainly regulated by CL synthase activity. The differences in these reactions probably reflect different functions of PG and CL in prokaryotes and mitochondria.In Escherichia coli, the enzymes that catalyze the synthesis of CL have been characterized biochemically, and the genes encoding these enzymes have been cloned. Although disruption of the cls gene (encoding CL synthase) is not lethal, bacterial strains bearing a null allele of pgsA (encoding PGP synthase) are inviable (8, 9). Interestingly, bacterial cls null mutants do synthesize CL, presumably by another enzyme. These experiments suggest that the anionic phospholipids PG and/or CL are essential for bacterial viability.

show abstract

mentioning

confidence: 99%

Absence of Cardiolipin in the crd1 Null Mutant Results in Decreased Mitochondrial Membrane Potential and Reduced Mitochondrial Function

Jiang¹,

Ryan²,

Schlame³

et al. 2000

Journal of Biological Chemistry

370

386

View full text Add to dashboard Cite

show abstract

“…In the yeast Saccharomyces cerevisiae, CL is required for cytochrome oxidase (CO) activity (41,42) and may be involved in import of proteins into the mitochondrion (10,11). In higher eucaryotes, CL is an effector of the cytochrome P-450-dependent cholesterol sidechain cleavage enzyme (31) and is required for activities of CO (34) and the mitochondrial phosphate carrier protein (21).…”

mentioning

confidence: 99%

Regulation of phosphatidylglycerolphosphate synthase in Saccharomyces cerevisiae by factors affecting mitochondrial development

et al. 1991

View full text Add to dashboard Cite

Phosphatidylglycerolphosphate synthase (PGPS; CDP-diacylglycerol glycerol 3-phosphate 3-phosphatidyltransferase; EC 2.7.8.5) catalyzes the first step in the synthesis of cardiolipin, an acidic phospholipid found in the mitochondrial inner membrane. In the yeast Saccharomyces cerevisiae, PGPS expression is coordinately regulated with general phospholipid synthesis and is repressed when cells are grown in the presence of the phospholipid precursor inositol (M. L. Greenberg, S. Hubbell, and C. Lam, Mol. Cell. Biol. 8:47734779, 1988). In this study, we examined the regulation of PGPS in growth conditions affecting mitochondrial development (carbon source, growth stage, and oxygen availability) and in strains with genetic lesions affecting mitochondrial function. PGPS derepressed two-to threefold when cells were grown in a nonfermentable carbon source (glycerol-ethanol) Cardiolipin (CL) is found only in the mitochondrial inner membrane (7,9,20) and is necessary for several aspects of mitochondrial function. In the yeast Saccharomyces cerevisiae, CL is required for cytochrome oxidase (CO) activity (41, 42) and may be involved in import of proteins into the mitochondrion (10, 11). In higher eucaryotes, CL is an effector of the cytochrome P-450-dependent cholesterol sidechain cleavage enzyme (31) and is required for activities of CO (34) and the mitochondrial phosphate carrier protein (21). An understanding of the regulation of CL biosynthesis would therefore provide insight into mitochondrial membrane biogenesis as well as the role played by this phospholipid in mitochondrial function.The synthesis of CL involves three sequential reactions (7, 28, 37). The enzyme phosphatidylglycerolphosphate synthase (PGPS) catalyzes the committed step in CL synthesis, involving the conversion of the liponucleotide CDP-diglyceride (CDP-DG) and glycerol 3-phosphate to phosphatidylglycerolphosphate (PGP). PGP phosphatase (PGPase) dephosphorylates PGP to phosphatidylglycerol, which subsequently is converted to CL by CL synthase (CLS). In procaryotes, CL is synthesized from two molecules of phosphatidylglycerol, while in higher eucaryotes, the CLS reaction involves the condensation of phosphatidylglycerol and CDP-DG. Tamai and Greenberg (39) have recently shown that S. cerevisiae, * Corresponding author. like higher eucaryotes, utilizes CDP-DG as a substrate in the synthesis of CL.We initially postulated that mitochondrial phospholipid synthesis may be affected by at least two sets of factors: (i) those that affect general phospholipid synthesis and (ii) those that affect mitochondrial development. In a previous study (14), our laboratory showed that expression of PGPS in S. cerevisiae is indeed regulated by the water-soluble phospholipid precursors inositol and choline. These precursors also repress the enzymes of the phosphatidylinositol (PI) and phosphatidylcholine (PC) branches of phospholipid synthesis (6). However, inositol repression of PGPS is not mediated by the same genetic regulatory circuit that controls the PI and PC branche...

show abstract

“…In S. cerevisiae, the phospholipid cardiolipin (CL) is found only in the mitochondrial membrane and is required for mitochondrial function (14,19). Therefore, we can use this phospholipid as a marker for the study of mitochondrion-specific membrane biogenesis.…”

mentioning

confidence: 99%

Phosphatidylglycerolphosphate synthase expression in Schizosaccharomyces pombe is regulated by the phospholipid precursors inositol and choline

1991

View full text Add to dashboard Cite

The enzyme phosphatidylglycerolphosphate synthase (PGPS; CDP-diacylglycerol glycerol 3-phosphate 3-phosphatidyltransferase; EC 2.7.8.5) catalyzes the committed step in the cardiolipin biosynthetic pathway. To study the regulation of PGPS in Schizosacchlaromyces pombe, we characterized the enzyme biochemically.Maximum activity occurred in the presence of 6 mM Triton X-100 at pH 7.5. The apparent Km values for CDP-diacylglycerol and glycerol 3-phosphate were 130 and 26 ,M, respectively. Optimal activity was at 35°C, and enzyme activity was labile above 40°C. Thioreactive agents were inhibitory to PGPS activity. To determine whether S. pombe PGPS is regulated by phospholipid precursors, we examined the time-dependent expression of PGPS upon inositol and choline starvation. Starvation for inositol resulted in a threefold increase in PGPS expression in wild-type cells. In chol and cho2 mutants, which are blocked in phosphatidylcholine synthesis, starvation for choline resulted in transient derepression of PGPS expression. In choline auxotrophs starved for inositol, PGPS was derepressed 2.5-to 3-fold in the presence of choline and less or not at all in the absence of choline. This is the first description of PGPS regulation in S. pombe and the first demonstration of inositol-mediated regulation in the inositol-requiring yeast species.Inositol plays a crucial role in general phospholipid metabolism in the budding yeast Saccharomyces cerevisiae (3,11,15). In this organism, inositol can be synthesized from glucose 6-phosphate in a reaction catalyzed by inositol 1-phosphate synthase (5). Inositol is utilized in the synthesis of the membrane phospholipid phosphatidylinositol (PI) (Fig. 1) (8). In addition, inositol acts as a regulator of phospholipid synthesis by repressing levels of the PI and phosphatidylcholine (PC) branch enzymes inositol 1-phosphate synthase, CDP-diacylglycerol (CDP-DG) synthase, phosphatidylserine (PS) synthase, PS decarboxylase, and the phospholipid N-methyltransferases (3). Inositol regulation of these enzymes is dependent on PC synthesis as well as the interaction of three unlinked regulatory genes (IN02-IN04-OPII). Choline, which can be used to synthesize PC via the Kennedy pathway, represses inositol 1-phosphate synthase, PS synthase, and the N-methyltransferases, although to a much lesser extent than inositol does. Repression by choline is only apparent in cells grown in the presence of inositol (3,13,21,22).We have made use of the knowledge gained from the genetic and molecular dissection of general phospholipid synthesis to understand how the mitochondrial membrane is synthesized. In S. cerevisiae, the phospholipid cardiolipin (CL) is found only in the mitochondrial membrane and is required for mitochondrial function (14,19). Therefore, we can use this phospholipid as a marker for the study of mitochondrion-specific membrane biogenesis. The enzyme phosphatidylglycerolphosphate synthase (PGPS; CDP-DG sn-glycerol 3-phosphate 3-phosphatidyltransferase; EC 2.7.8.5) is located in the mitochondrial...

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Functional Importance of Mitochondrial Cardiolipin in Yeast Cytochrome c Oxidase Activity

Cited by 12 publications

References 13 publications

Absence of Cardiolipin in the crd1 Null Mutant Results in Decreased Mitochondrial Membrane Potential and Reduced Mitochondrial Function

Absence of Cardiolipin in the crd1 Null Mutant Results in Decreased Mitochondrial Membrane Potential and Reduced Mitochondrial Function

Regulation of phosphatidylglycerolphosphate synthase in Saccharomyces cerevisiae by factors affecting mitochondrial development

Phosphatidylglycerolphosphate synthase expression in Schizosaccharomyces pombe is regulated by the phospholipid precursors inositol and choline

Contact Info

Product

Resources

About