Phospholipid Acyl Chain Diversity Controls the Tissue-Specific Assembly of Mitochondrial Cardiolipins

Oemer, Gregor; Koch, Jakob; Wohlfarter, Yvonne; Alam, Mohammad Tauqeer; Lackner, Katharina; Sailer, S; Neumann, Lukas; Lindner, Herbert; Watschinger, Katrin; Haltmeier, Markus; Werner, Ernst R.; Zschocke, Johannes; Keller, Markus A.

doi:10.1016/j.celrep.2020.02.115

Cited by 74 publications

(109 citation statements)

References 68 publications

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“…For instance, CL profile is highly varied in the mammalian brain but is more homogeneous in terms of molecular species in other tissues, including the heart (Kiebish et al, 2008;Schlame et al, 2005;Tyurina et al, 2014). The phospholipid environment, particularly the balance of linoleoyl (18:2) and oleoyl (18:1) levels, is a key determinant of the CL landscape across tissues (Oemer et al, 2020). CL remodeling is initiated by a phospholipase, removing an acyl chain from CL to form monolyso-CL (MLCL).…”

Section: Metabolismmentioning

confidence: 99%

Phospholipid ebb and flow makes mitochondria go

Acoba

Senoo

Claypool

2020

Journal of Cell Biology

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Mitochondria, so much more than just being energy factories, also have the capacity to synthesize macromolecules including phospholipids, particularly cardiolipin (CL) and phosphatidylethanolamine (PE). Phospholipids are vital constituents of mitochondrial membranes, impacting the plethora of functions performed by this organelle. Hence, the orchestrated movement of phospholipids to and from the mitochondrion is essential for cellular integrity. In this review, we capture recent advances in the field of mitochondrial phospholipid biosynthesis and trafficking, highlighting the significance of interorganellar communication, intramitochondrial contact sites, and lipid transfer proteins in maintaining membrane homeostasis. We then discuss the physiological functions of CL and PE, specifically how they associate with protein complexes in mitochondrial membranes to support bioenergetics and maintain mitochondrial architecture.

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Section: Metabolismmentioning

confidence: 99%

Phospholipid ebb and flow makes mitochondria go

Acoba

Senoo

Claypool

2020

Journal of Cell Biology

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“…The acyl chain content of MLCL in BTHS cells has a low degree of unsaturation [ 28 , 29 ] whereas remodelled, mature CL has a higher level of unsaturation, although this does vary between tissue types [ 30 ]: (18:2) 4 acyl chain content is particularly tightly controlled in mammalian cardiac tissue [ 31 ], while brain CL is more diverse [ 32–34 ].…”

Section: The Structure and Physical Properties Of Mlclmentioning

confidence: 99%

Monolysocardiolipin (MLCL) interactions with mitochondrial membrane proteins

Duncan

2020

Biochemical Society Transactions

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Monolysocardiolipin (MLCL) is a three-tailed variant of cardiolipin (CL), the signature lipid of mitochondria. MLCL is not normally found in healthy tissue but accumulates in mitochondria of people with Barth syndrome (BTHS), with an overall increase in the MLCL:CL ratio. The reason for MLCL accumulation remains to be fully understood. The effect of MLCL build-up and decreased CL content in causing the characteristics of BTHS are also unclear. In both cases, an understanding of the nature of MLCL interaction with mitochondrial proteins will be key. Recent work has shown that MLCL associates less tightly than CL with proteins in the mitochondrial inner membrane, suggesting that MLCL accumulation is a result of CL degradation, and that the lack of MLCL–protein interactions compromises the stability of the protein-dense mitochondrial inner membrane, leading to a decrease in optimal respiration. There is some data on MLCL–protein interactions for proteins involved in the respiratory chain and in apoptosis, but there remains much to be understood regarding the nature of MLCL–protein interactions. Recent developments in structural, analytical and computational approaches mean that these investigations are now possible. Such an understanding will be key to further insights into how MLCL accumulation impacts mitochondrial membranes. In turn, these insights will help to support the development of therapies for people with BTHS and give a broader understanding of other diseases involving defective CL content.

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“…Phospholipids were extracted and analyzed by LC-MS/MS as described previously 13 and the retention time and m/z characteristics of all features were compared. While some m/z overlap problems between plasmenyl-PC and phosphatidylserines or PE species can be readily resolved by measuring with mass resolutions larger than 21k and 14k, respectively, the truly isobaric nature of plasmanyl and plasmenyl PE/PC species remains a major analytical challenge.…”

Section: Resultsmentioning

confidence: 99%

“…The PC/PE analysis was performed as described in 33 , with the modifications described in 13 . 10 µl of the samples were injected by a Dionex Ultimate 3000 HPLC (Thermofisher Scientific Inc, Waltham, USA) with a flowrate of 0.4 ml/min and a column oven temperature of 50 °C.…”

Section: Lc-ms/ms Analysismentioning

confidence: 99%

Unequivocal mapping of molecular ether lipid species by LC-MS/MS in plasmalogen-deficient mice

Koch

Lackner

Wohlfarter

et al. 2020

Preprint

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Deficient ether lipid biosynthesis in rhizomelic chondrodysplasia punctata and other disorders is associated with a wide range of severe symptoms including small stature with proximal shortening of the limbs, contractures, facial dysmorphism, congenital cataracts, ichthyosis, spasticity, microcephaly, and mental disability. Mouse models are available but show less severe symptoms. In both humans and mice it has remained elusive which of the symptoms can be attributed to lack of plasmanyl or plasmenyl ether lipids. The latter compounds, better known as plasmalogens, harbor a vinyl ether double bond conferring special chemical and physical properties. Discrimination between plasmanyl and plasmenyl ether lipids is a major analytical challenge, especially in complex lipid extracts with many isobaric species. Consequently, these lipids are often neglected also in recent lipidomic studies. Here we present a comprehensive LC-MS/MS based approach that allows unequivocal distinction of these two lipid subclasses based on their chromatographic properties. The method was validated using a novel plasmalogen-deficient mouse model which lacks plasmanylethanolamine desaturase and therefore cannot form plasmenyl ether lipids. We demonstrate that plasmanylethanolamine desaturase deficiency causes an accumulation of plasmanyl species, a little studied but biologically important substance class.

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Phospholipid Acyl Chain Diversity Controls the Tissue-Specific Assembly of Mitochondrial Cardiolipins

Cited by 74 publications

References 68 publications

Phospholipid ebb and flow makes mitochondria go

Phospholipid ebb and flow makes mitochondria go

Monolysocardiolipin (MLCL) interactions with mitochondrial membrane proteins

Unequivocal mapping of molecular ether lipid species by LC-MS/MS in plasmalogen-deficient mice

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