Molecular structural diversity of mitochondrial cardiolipins

Oemer, Gregor; Lackner, Katharina; Muigg, Katharina; Krumschnabel, Gerhard; Watschinger, Katrin; Sailer, S; Lindner, Herbert; Gnaiger, Erich; Wortmann, Saskia B.; Werner, Ernst R.; Zschocke, Johannes; Keller, Markus A.

doi:10.1073/pnas.1719407115

Cited by 85 publications

(132 citation statements)

References 33 publications

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“…For example, ClsA colocalizes with its cardiolipin products (Romantsov et al ., ). In the same way, cardiolipins are closely associated with cristae in mitochondria (Ikon and Ryan, ; Schlame and Greenberg, ; Oemer et al ., ). These molecules can act as seeds to induce local curvature in an autocatalytic way.…”

Section: An Open List Of Basic Cellular Maxwell's Demonsmentioning

confidence: 97%

Omnipresent Maxwell's demons orchestrate information management in living cells

Boël

Danot

Lorenzo

et al. 2019

Microbial Biotechnology

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Summary The development of synthetic biology calls for accurate understanding of the critical functions that allow construction and operation of a living cell. Besides coding for ubiquitous structures, minimal genomes encode a wealth of functions that dissipate energy in an unanticipated way. Analysis of these functions shows that they are meant to manage information under conditions when discrimination of substrates in a noisy background is preferred over a simple recognition process. We show here that many of these functions, including transporters and the ribosome construction machinery, behave as would behave a material implementation of the information‐managing agent theorized by Maxwell almost 150 years ago and commonly known as Maxwell's demon (MxD). A core gene set encoding these functions belongs to the minimal genome required to allow the construction of an autonomous cell. These MxDs allow the cell to perform computations in an energy‐efficient way that is vastly better than our contemporary computers.

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Section: An Open List Of Basic Cellular Maxwell's Demonsmentioning

confidence: 97%

Omnipresent Maxwell's demons orchestrate information management in living cells

Boël

Danot

Lorenzo

et al. 2019

Microbial Biotechnology

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“…This unveils the existence of distinct CL content thresholds to achieve complementary roles of CL in ATP production. The two last steps of CL synthesis occur within mitochondria, first CL synthase catalyses binding of CDP-diacylglycerol to phosphatidylglycerol to form CL, and then Tafazzin remodels the acylchain composition in the heart and skeletal muscles, which results in an enrichment of linoleoyl chains (C18:2, ω-6) in CL (Oemer et al, 2018). The functional importance of the latter reaction is illustrated by Barth syndrome, characterized by a life-threatening infantile dilated cardiomyopathy, which develops associated with Tafazzin deficiency (Barth et al, 1983;Ikon and Ryan, 2017a).…”

Section: Discussionmentioning

confidence: 99%

Alteration of cardiolipin-dependent mitochondrial coupling in muscle protects against obesity

Prola

Blondelle

Vandestienne

et al. 2019

Preprint

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The tubular shape of mitochondrial cristae depends upon a specific composition of the inner mitochondrial membrane, including cardiolipin that allows strong curvature and promotes optimal organization of ATP synthase. Here we identify Hacd1, which encodes an enzyme involved in very long chain fatty acid biosynthesis, as a key regulator of composition, structure and functional properties of mitochondrial membranes in muscle. In Hacd1-deficient mice, the reduced cardiolipin content was associated with dilation of cristae and caused defective phosphorylating respiration, characterized by absence of proton leak and oxidative stress.The skeletal muscle-specific mitochondrial coupling defect produced a global elevation in basal energy expenditure with increased carbohydrate and lipid catabolism, despite decreased muscle mass and locomotor capacities. Mice were protected against diet-induced obesity despite reduced muscle activity, providing an in vivo proof of concept that reducing mitochondrial coupling efficiency in skeletal muscle might be an actionable mechanism in metabolic disease conditions.

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“…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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Molecular structural diversity of mitochondrial cardiolipins

Cited by 85 publications

References 33 publications

Omnipresent Maxwell's demons orchestrate information management in living cells

Omnipresent Maxwell's demons orchestrate information management in living cells

Alteration of cardiolipin-dependent mitochondrial coupling in muscle protects against obesity

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

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