Mitochondrial contact sites. Lipid composition and dynamics.

Ardail, Dominique; Privat, Jean Paul; Egret‐Charlier, Marguerite; Levrat, Christiane; Lermé, F.; Louisot, Pierre

doi:10.1016/s0021-9258(17)30583-5

Cited by 396 publications

(95 citation statements)

References 32 publications

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“…The present study adds a new task in this mechanism, by demonstrating that CL is also present in MAM fractions following autophagy triggering and interacts with key molecules involved in autophagosome formation. The presence of CL in the MAM fraction is not surprising, since it is present in the contact sites formed between the inner and outer membranes [6]. The presence of CL in MAM is in agreement with Li et al [46], who reported that MAM is a major site for phospholipid synthesis and traffic, including CL.…”

Section: Discussionsupporting

confidence: 89%

“…CL is required for optimal mitochondrial function and is known to give essential structural and functional support to several proteins involved in mitochondrial processes, including respiration and energy conversion [3][4][5]. Although the distribution of CL is mostly confined to the IMM, it also distributes in the outer mitochondrial membrane (OMM), specifically in the contact sites formed between the inner and outer membranes, where its content is even higher (about 27% of total phospholipids) [6]. These contact sites represent a relevant portion of mitochondrial membrane, since about 115 such sites were calculated in one isolated mitochondrion (ranging from 78 to 270 depending on cell type) [7].…”

Section: Introductionmentioning

confidence: 99%

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The Role of Cardiolipin as a Scaffold Mitochondrial Phospholipid in Autophagosome Formation: In Vitro Evidence

et al. 2021

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Cardiolipin (CL) is a hallmark phospholipid localized within the inner mitochondrial membrane. Upon several mitochondrial stress conditions, CL is translocated to specialized platforms, where it may play a role in signaling events to promote mitophagy and apoptosis. Recent studies characterized the molecular composition of MAM-associated lipid microdomains and their implications in regulating the autophagic process. In this study we analyzed the presence of CL within MAMs following autophagic stimulus and the possible implication of raft-like microdomains enriched in CL as a signaling platform in autophagosome formation. Human 2FTGH fibroblasts and SKNB-E-2 cells were stimulated under nutrient deprivation with HBSS. MAM fraction was obtained by an ultracentrifugation procedure and analyzed by HPTLC immunostaining. CL interactions with mitofusin2 (MFN2), calnexin (CANX) and AMBRA1 were analyzed by scanning confocal microscopy and coimmunoprecipitation. The analysis revealed that CL accumulates in MAMs fractions following autophagic stimulus, where it interacts with MFN2 and CANX. It associates with AMBRA1, which in turn interacts with BECN1 and WIPI1. This study demonstrates that CL is present in MAM fractions following autophagy triggering and interacts with the multimolecular complex (AMBRA1/BECN1/WIPI1) involved in autophagosome formation. It may have both structural and functional implications in the pathophysiology of neurodegenerative disease(s).

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

The Role of Cardiolipin as a Scaffold Mitochondrial Phospholipid in Autophagosome Formation: In Vitro Evidence

et al. 2021

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“…Normally, CL constitutes about 25 mol% of mitochondrial membrane lipids (Daum 1985). In eukaryotic cells, over 65% of CL is predominantly confined to the inner leaflet of the IMM (Ardail et al 1990;Krebs et al 1979). However, Charleen T. Chu and colleagues found that both the content and species of CL in the OMM were increased in mitophagy-inducing cells.…”

Section: Translocation Of CL In Mitochondria Membranesmentioning

confidence: 99%

“…Both Bid and tBid have a high-affinity binding domain for CL (Ardail et al 1990;Gonzalvez et al 2005;Lutter et al 2000;Tyurin et al 2006). MS data have demonstrated that the α4-α6 domain of Bid is the targeting sequence (Kim et al 2004).…”

Section: Is Necessary For Mmp Formationmentioning

confidence: 99%

“…The structure of CL is characterized by a glycerol backbone connected to two phosphatidyl lipids. This structure is more flexible than regular phospholipids because CL possesses two chiral carbons and four fatty acyl chains that are usually polyunsaturated (Ardail et al 1990). CL on the mitochondrial membranes can be induced to cause a negative membrane curvature, and this makes CL a perfect brick with which to build the inner folded cristae (Acehan et al 2009;Schlame 2012;Xu et al 2006a).…”

Section: Introduction To Cardiolipinmentioning

confidence: 99%

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Cardiolipin and Its Different Properties in Mitophagy and Apoptosis

Tsoi

et al. 2015

J Histochem Cytochem.

126

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SummaryCardiolipin (CL) is a unique dimeric phospholipid that exists almost exclusively in the inner mitochondrial membrane (IMM) in eukaryotic cells. Two chiral carbons and four fatty acyl chains in CL result in a flexible body allowing interactions with respiratory chain complexes and mitochondrial substrate carriers. Due to its high content of unsaturated fatty acids, CL is particularly prone to reactive oxygen species (ROS)-induced oxidative attacks. Under mild mitochondrial damage, CL is redistributed to the outer mitochondrial membrane (OMM) and serves as a recognition signal for dysfunctional mitochondria, which are rapidly sequestered by autophagosomes. However, peroxidation of CL is far greater in response to severe stress than under normal or mild-damage conditions. The accumulation of oxidized CL on the OMM results in recruitment of Bax and formation of the mitochondrial permeability transition pore (MPTP), which releases Cytochrome c (Cyt c) from mitochondria. Over the past decade, the significance of CL in the function of mitochondrial bioenergy has been explored. Moreover, approaches to analyzing CL have become more effective and accurate. In this review, we discuss the unique structural features of CL as well as the current understanding of CL-based molecular mechanisms of mitophagy and apoptosis. Keywords apoptosis, cardiolipin, mitophagy, oxidation, translocation 302Li et al. such as phosphatidylethanolamine (PE) and phosphatidylserine (PS)?The dimeric structure and polyunsaturated fatty acyl chains of CL may be responsible for its ability to switch between lamellar and negative curvature profiles. The biosynthesis of CL is a little more complex than that of PE and PS and involves two pathways: de novo synthesis and remodeling steps (Hatch 1998;Schlame et al. 2000) (Fig. 1). The de novo reactions originate from phosphatidic acid (PA). First, PA is transformed into cytidine diphosphate-diacylglycerol (CDP-DAG) in the presence of CDP-DAG synthase (Houtkooper and Vaz 2008). Then, CDP-DAG is converted to phosphatidylglycerol phosphate (PGP) by displacement of the cytidine monophosphate (CMP) moiety by sn-glycerol-3-phosphate through the activity of the PGP synthase. This is followed by a dephosphorylation reaction to produce PG (Chang et al. 1998;Stanacev et al. 1967). Finally, the combination of PG and CDP-DAG yields CL through the activity of cardiolipin synthase (CLS) (Chicco and Sparagna 2007;Lu et al. 2006). On the other hand, PE and PS possess relatively simple structures composed of a glycerol with two fatty acyl chains. Two chiral carbons on the two side glycerols of CL allow the four acyl chains to combine in different spatial locations. These distinct spatial structures may have important roles in the fluidity of cristae as well as in the fixation of proteins in mitochondrial membranes.CLS has no preference for certain acyl chains, indicating that post-synthetic remodeling is essential to produce specific polyunsaturated fatty acyl chains in CL. Remodeling is a cycle of deacylation and rea...

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The Outer Mitochondrial Membrane Pore (Voltage‐Dependent Anion Channel)

Vyssokikh

Brdiczka

2008

Protein Science Encyclopedia

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Originally published in: Bacterial and Eukaryotic Porins. Edited by Roland Benz. Copyright © 2005 Wiley‐VCH Verlag GmbH & Co. KGaA Weinheim. Print ISBN: 3‐527‐30775‐3 The sections in this article are Introduction Structure and Isotypes of VDAC The Influence of Phospholipids on VDAC Structure VDAC Conductance and Ion Selectivity Physiological Significance of the Voltage Dependence Porins as Specific Binding Sites VDAC senses Inner Membrane Functions in the Contact Site Cytochrome c is a Component of the Contact Sites Isolation and Characterization of VDAC‐ANT Complexes Reconstitution of VDAC‐ANT Complexes Importance of Metabolic Channeling in Regulation of Energy Metabolism The VDAC‐ANT Complex as Permeability Transition Pore The VDAC‐ANT Complex as a Target for Bax‐dependent Cytochrome c Release The VDAC–ANT Complexes contain Cytochrome c The Importance of the Kinases in Regulation of Apoptosis Suppression of Bax‐dependent Cytochrome c Release and Permeability Transition by Hexokinase Suppression of Permeability Transition by Mitochondrial Creatine Kinase Conclusion

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Mitochondrial contact sites. Lipid composition and dynamics.

Cited by 396 publications

References 32 publications

The Role of Cardiolipin as a Scaffold Mitochondrial Phospholipid in Autophagosome Formation: In Vitro Evidence

The Role of Cardiolipin as a Scaffold Mitochondrial Phospholipid in Autophagosome Formation: In Vitro Evidence

Cardiolipin and Its Different Properties in Mitophagy and Apoptosis

The Outer Mitochondrial Membrane Pore (Voltage‐Dependent Anion Channel)

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