Microanalysis of cardiolipin in small biopsies including skeletal muscle from patients with mitochondrial disease

Schlame, Michael; Shanske, Sara; Doty, Steven B.; König, Thomas; Sculco, Thomas P.; DiMauro, Salvatore; Blanck, Thomas J. J.

doi:10.1016/s0022-2275(20)33404-0

Cited by 65 publications

(8 citation statements)

References 32 publications

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“…In higher eukaryotes, CL is composed exclusively of fatty acids with 18 C atoms, − distributed as summarized in Table , with unsaturated acids the most abundant (∼80%) . This observation is of crucial importance because oxidation of this phospholipid is one of the principal outcomes regarding its interaction with cyt c , as will be discussed in the next sections.…”

Section: Alternative Functions Of Cytochrome Cmentioning

confidence: 99%

Multifunctional Cytochrome c: Learning New Tricks from an Old Dog

et al. 2017

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Cytochrome c (cyt c) is a small soluble heme protein characterized by a relatively flexible structure, particularly in the ferric form, such that it is able to sample a broad conformational space. Depending on the specific conditions, interactions, and cellular localization, different conformations may be stabilized, which differ in structure, redox properties, binding affinities, and enzymatic activity. The primary function is electron shuttling in oxidative phosphorylation, and is exerted by the so-called native cyt c in the intermembrane mitochondrial space of healthy cells. Under pro-apoptotic conditions, however, cyt c gains cardiolipin peroxidase activity, translocates into the cytosol to engage in the intrinsic apoptotic pathway, and enters the nucleus where it impedes nucleosome assembly. Other reported functions include cytosolic redox sensing and involvement in the mitochondrial oxidative folding machinery. Moreover, post-translational modifications such as nitration, phosphorylation, and sulfoxidation of specific amino acids induce alternative conformations with differential properties, at least in vitro. Similar structural and functional alterations are elicited by biologically significant electric fields and by naturally occurring mutations of human cyt c that, along with mutations at the level of the maturation system, are associated with specific diseases. Here, we summarize current knowledge and recent advances in understanding the different structural, dynamic, and thermodynamic factors that regulate the primary electron transfer function, as well as alternative functions and conformations of cyt c. Finally, we present recent technological applications of this moonlighting protein.

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Section: Alternative Functions Of Cytochrome Cmentioning

confidence: 99%

Multifunctional Cytochrome c: Learning New Tricks from an Old Dog

et al. 2017

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“…Extraction : CL was extracted from the samples by a modified Folch extraction procedure. 16 Briefly, 50 ng of tetra-myristoyl-CL ((C14:0) 4 -CL; Avanti Polar Lipids, Inc) was added as the internal standard to 10 μ L incubation mixture. The extraction of CL was carried out with chloroform/methanol (2/1) containing 0.05% butyl-hydroxy-toluene as antioxidant.…”

Section: Methodsmentioning

confidence: 99%

“…Aqueous and lipid phases were separated by adding 0.01 mol/L HCl followed by intensive shaking and subsequent centrifugation. The lower lipid phase was collected, dried under nitrogen atmosphere and acidified as described by Schlame et al 16 Ice-cold methanol (2 mL), chloroform (1 mL) and 0.1 mol/L HCl (1 mL) were added to the sample. The solution was intensively mixed and incubated for five minutes on ice.…”

Section: Methodsmentioning

confidence: 99%

Composition of molecular cardiolipin species correlates with proliferation of lymphocytes

Schild

Lendeckel

Gardemann

et al. 2012

Exp Biol Med (Maywood)

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The mitochondrial phospholipid cardiolipin (CL) is required for oxidative phosphorylation. Oxidation of CL results in the disruption of CL-cytochrome c binding and the induction of apoptosis. Large variations in the acyl-chain residues of CL have been reported, but evidence as to whether these variants exert distinct biological effects has been limited. We have studied the acyl-chain composition of CL in lymphocytes, and found marked differences between highly and slowly proliferating cells. In fast growing cells, we detected a decreased number of double bonds, and a higher amount of C16 acyl-chain residues in CL, compared with slower growing cells. However, fewer C18 acyl-chain residues were found in CL from fast growing cells compared with slower proliferating cells. Our results suggest a functional link between acyl-chain composition of CL and cell proliferation.

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“…However, both the amount and the types of CL are varied in different species, cells and membranes, which is still unexplainable so far. 23 For example, early studies 24 have shown that around 25% of all the mitochondria lipids under physiological conditions are CLs. Furthermore, there is an unbalanced distribution between the IMM and OMM in which more than 65% of CLs are inset into the IMM.…”

Section: Cyt C Cl and Mitochondriamentioning

confidence: 99%

Double-edged sword in cells: chemical biology studies of the vital role of cytochrome c in the intrinsic pre-apoptotic mitochondria leakage pathway

et al. 2015

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Besides functioning as an electron transporter in the mitochondrial electron transport chain, cytochrome c (cyt c) is also one of the determinants in the execution of cell death. The interaction between cyt c and lipids has long been of great interest in biological systems, while the study of cyt c has attracted even more attention since its new function in apoptosis was discovered. Theories on the cause-effect signaling pathways have been proposed. However, until recently, some of the detailed parts have remained poorly understood in the big picture of cyt c-mediated apoptosis. In the past few years, new labelling, monitoring and detecting methods as well as in vitro model systems such as cyt c-cardiolipin (CL) or cyt c-membrane systems have been developed to overcome these drawbacks. The discovery of the versatile roles of cyt c in metabolic as well as apoptotic processes suggests cyt c per se as a potential drug target. In this review, we divide the whole cyt c-mediated pre-apoptotic mitochondrial leakage process into several sections in a chronological order and summarize the recent discoveries and hypotheses. With the combinatorial effort of modern interdisciplinary subjects such as chemical biology, bio-inorganic chemistry, structural biology and physical organic chemistry, we expect that researches in this field will shed light on our understanding of the whole intrinsic apoptotic process, and further contribute to health sciences.

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Microanalysis of cardiolipin in small biopsies including skeletal muscle from patients with mitochondrial disease

Cited by 65 publications

References 32 publications

Multifunctional Cytochrome c: Learning New Tricks from an Old Dog

Multifunctional Cytochrome c: Learning New Tricks from an Old Dog

Composition of molecular cardiolipin species correlates with proliferation of lymphocytes

Double-edged sword in cells: chemical biology studies of the vital role of cytochrome c in the intrinsic pre-apoptotic mitochondria leakage pathway

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