Deacylation on the matrix side of the mitochondrial inner membrane regulates cardiolipin remodeling

Baile, Matthew G.; Whited, Kevin; Claypool, Steven M.

doi:10.1091/mbc.e13-03-0121

Cited by 63 publications

(62 citation statements)

References 98 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, CL remodeling may require the coordinated action of phospholipase(s) and transacylase(s), such as tafazzin. Nevertheless, because tafazzin and Cld1 (both contain no transmembrane segment) are associated with the intermembrane space-facing and matrix-facing leaflets of the mitochondrial inner membrane, respectively (4,45), MLCL generated by Cld1 must be transported to the intermembrane space-facing leaflet to gain access to tafazzin, suggesting the existence of an as yet unidentified protein(s) capable of redistributing MLCL across the inner membrane. Further studies are needed to establish all of the involved players and elucidate their roles in CL remodeling in mitochondria.…”

Section: Discussionmentioning

confidence: 99%

Mechanism for Remodeling of the Acyl Chain Composition of Cardiolipin Catalyzed by Saccharomyces cerevisiae Tafazzin

Abe

Hasegawa

Oku

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Remodeling of the acyl chains of cardiolipin (CL) is responsible for final molecular composition of mature CL after de novo CL synthesis in mitochondria. Yeast Saccharomyces cerevisiae undergoes tafazzin-mediated CL remodeling, in which tafazzin serves as a transacylase from phospholipids to monolyso-CL (MLCL). In light of the diversity of the acyl compositions of mature CL between different organisms, the mechanism underlying tafazzin-mediated transacylation remains to be elucidated. We investigated the mechanism responsible for transacylation using purified S. cerevisiae tafazzin with liposomes composed of various sets of acyl donors and acceptors. The results revealed that tafazzin efficiently catalyzes transacylation in liposomal membranes with highly ordered lipid bilayer structure. Tafazzin elicited unique acyl chain specificity against phosphatidylcholine (PC) as follows: linoleoyl (18:2) > oleoyl (18:1) ‫؍‬ palmitoleoyl (16:1) > > palmitoyl (16:0). In these reactions, tafazzin selectively removed the sn-2 acyl chain of PC and transferred it into the sn-1 and sn-2 positions of MLCL isomers at equivalent rates. We demonstrated for the first time that MLCL and dilyso-CL have inherent abilities to function as an acyl donor to monolyso-PC and acyl acceptor from PC, respectively. Furthermore, a Barth syndrome-associated tafazzin mutant (H77Q) was shown to completely lack the catalytic activity in our assay. It is difficult to reconcile the present results with the so-called thermodynamic remodeling hypothesis, which premises that tafazzin reacylates MLCL by unsaturated acyl chains only in disordered non-bilayer lipid domain. The acyl specificity of tafazzin may be one of the factors that determine the acyl composition of mature CL in S. cerevisiae mitochondria.

show abstract

Section: Discussionmentioning

confidence: 99%

Mechanism for Remodeling of the Acyl Chain Composition of Cardiolipin Catalyzed by Saccharomyces cerevisiae Tafazzin

Abe

Hasegawa

Oku

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Although different approaches have been used, this proposed model is similar to the model described in Baile et al (39), in which they suggested a feedback loop between oxidative phosphorylation and CL remodeling. Specifically, they found that CLD1 expression is regulated by carbon sources, and the activity of Cld1 is increased by dissipating the mitochondrial membrane potential (39). They suggested that CL remodeling functions to increase oxidative phosphorylation efficiency and/or replace oxidized CL.…”

Section: Journal Of Biological Chemistrymentioning

confidence: 99%

“…Following the de novo synthesis of CL on the matrix side of the inner mitochondrial membrane, CL undergoes remodeling in which acyl chains are exchanged. In this process, CL is deacylated to monolysocardiolipin (MLCL) by the CL-specific lipase Cld1 on the matrix side of the inner mitochondrial membrane (38,39). MLCL is reacylated by the transacylase Taz1 in the mitochondrial periphery (40 -43).…”

Section: Cardiolipin (Cl)mentioning

confidence: 99%

Deletion of the Cardiolipin-specific Phospholipase Cld1 Rescues Growth and Life Span Defects in the Tafazzin Mutant

Lou

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Cardiolipin (CL) is deacylated by Cld1 to monolysocardiolipin, which is transacylated by tafazzin (Taz1) to form unsaturated CL. Results: Deletion of CLD1 rescues growth and respiration defects in taz1⌬, whereas overexpression is deleterious to growth and respiration. Conclusion: Decreased CL/MLCL, not decreased unsaturated CL, causes defects in tafazzin-deficient cells. Significance: Attenuation of CL phospholipases may potentially treat Barth syndrome.

show abstract

“…69 The presence of non-linoleic acyls disrupts the compact configuration of (C18:2) 4 -CL, paradoxically increasing the oxidative sensitivity of the asymmetric CL. 20 ALCAT1 is located in the endoplasmic reticulum, 70 suggesting that secondary CL remodeling may require mitochondria-endoplasmic reticulum interactions. Since secondary remodeling of CL by ALCAT1 is extramitochondrial, it is unlikely that regional defects would be present.…”

Section: Mitochondrial Morphology In the Aging Heartmentioning

confidence: 99%

Mitochondrial Metabolism in Aging Heart

Lesnefsky

Chen

Hoppel

2016

Circulation Research

262

207

View full text Add to dashboard Cite

Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III and IV, which account for the decrease in respiration. Furthermore, aging decreases mitochondrial content among the myofibrils. The end result is that in the interfibrillar area there is an approximate 50% decrease in mitochondrial function, affecting all substrates. The defective mitochondria persist in the aged heart, leading to enhanced oxidant production and oxidative injury and the activation of oxidant signaling for cell death. Aging defects in mitochondria represent new therapeutic targets, whether by manipulation of the mitochondrial proteome, modulation of electron transport, activation of biogenesis or mitophagy, or the regulation of mitochondrial fission and fusion. These mechanisms provide new ways to attenuate cardiac disease in elders by preemptive treatment of age-related defects, in contrast to the treatment of disease-induced dysfunction.

show abstract

Deacylation on the matrix side of the mitochondrial inner membrane regulates cardiolipin remodeling

Cited by 63 publications

References 98 publications

Mechanism for Remodeling of the Acyl Chain Composition of Cardiolipin Catalyzed by Saccharomyces cerevisiae Tafazzin

Mechanism for Remodeling of the Acyl Chain Composition of Cardiolipin Catalyzed by Saccharomyces cerevisiae Tafazzin

Deletion of the Cardiolipin-specific Phospholipase Cld1 Rescues Growth and Life Span Defects in the Tafazzin Mutant

Mitochondrial Metabolism in Aging Heart

Contact Info

Product

Resources

About