Distinct membrane properties are differentially influenced by cardiolipin content and acyl chain composition in biomimetic membranes

Pennington, Edward Ross; Fix, Amy; Sullivan, E. Madison; Brown, David A.; Kennedy, Anthony; Shaikh, Saame Raza

doi:10.1016/j.bbamem.2016.11.012

Cited by 31 publications

(33 citation statements)

References 85 publications

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“…Surface pressure-area isotherms ( π − A ) were obtained on a Mini LB Trough (KSV NIMA, Biolin Scientific, Stockholm, Sweden) using a Wilhelmy plate at a compression rate of 3.0 mm/min [35]. The trough was washed three times with 70% ethanol, Milli-Q water, and subphase (10 mM sodium phosphate buffer, pH 7.4) (Sigma-Aldrich, St. Louis, MO) before each run.…”

Section: Methodsmentioning

confidence: 99%

Murine diet-induced obesity remodels cardiac and liver mitochondrial phospholipid acyl chains with differential effects on respiratory enzyme activity

Sullivan

Fix

Crouch

et al. 2017

The Journal of Nutritional Biochemistry

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Cardiac phospholipids, notably cardiolipin, undergo acyl chain remodeling and/or loss of content in aging and cardiovascular diseases, which is postulated to mechanistically impair mitochondrial function. Less is known about how diet-induced obesity influences cardiac phospholipid acyl chain composition and thus mitochondrial responses. Here we first tested if a high fat diet remodeled murine cardiac mitochondrial phospholipid acyl chain composition and consequently disrupted membrane packing, supercomplex formation and respiratory enzyme activity. Mass spectrometry analyses revealed that mice consuming a high fat diet displayed 0.8–3.3 fold changes in cardiac acyl chain remodeling of cardiolipin, phosphatidylcholine, and phosphatidylethanolamine. Biophysical analysis of monolayers constructed from mitochondrial phospholipids of obese mice showed an impairment in the packing properties of the membrane compared to lean mice. However, the high fat diet, relative to the lean controls, had no influence on cardiac mitochondrial supercomplex formation, respiratory enzyme activity, and even respiration. To determine if the effects were tissue specific, we subsequently conducted select studies with liver tissue. Compared to the control diet, the high fat diet remodeled liver mitochondrial phospholipid acyl chain composition by 0.6–5.3 fold with notable increases in n-6 and n-3 polyunsaturation. The remodeling in the liver was accompanied by diminished complex I to III respiratory enzyme activity by 3.5 fold. Finally, qRT-PCR analyses demonstrated an upregulation of liver mRNA levels of tafazzin, which contributes to cardiolipin remodeling. Altogether, these results demonstrate that diet-induced obesity remodels acyl chains in the mitochondrial phospholipidome and exerts tissue specific impairments of respiratory enzyme activity.

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Section: Methodsmentioning

confidence: 99%

Murine diet-induced obesity remodels cardiac and liver mitochondrial phospholipid acyl chains with differential effects on respiratory enzyme activity

Sullivan

Fix

Crouch

et al. 2017

The Journal of Nutritional Biochemistry

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“…The fatty acid species composition of cardiolipin may be critical. Cardiolipin influences membrane biophysical properties and shapes the curvature of the mitochondrial cristae, which affects the assembly and function of the electron transport chain complexes and generation of ATP (Paradies, Paradies, Benedictis, Ruggiero, & Petrosillo, ; Pennington et al, ).…”

Section: Discussionmentioning

confidence: 99%

Low plasma lysophosphatidylcholines are associated with impaired mitochondrial oxidative capacity in adults in the Baltimore Longitudinal Study of Aging

et al. 2019

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The decrease in skeletal muscle mitochondrial oxidative capacity with age adversely affects muscle strength and physical performance. Factors that are associated with this decrease have not been well characterized. Low plasma lysophosphatidylcholines (LPC), a major class of systemic bioactive lipids, are predictive of aging phenotypes such as cognitive impairment and decline of gait speed in older adults. Therefore, we tested the hypothesis that low plasma LPC are associated with impaired skeletal muscle mitochondrial oxidative capacity. Skeletal muscle mitochondrial oxidative capacity was measured using in vivo phosphorus magnetic resonance spectroscopy (31P‐MRS) in 385 participants (256 women, 129 men), aged 24–97 years (mean 72.5) in the Baltimore Longitudinal Study of Aging. Postexercise recovery rate of phosphocreatine (PCr), kPCr, was used as a biomarker of mitochondrial oxidative capacity. Plasma LPC were measured using liquid chromatography–tandem mass spectrometry. Adults in the highest quartile of kPCr had higher plasma LPC 16:0 (p = 0.04), 16:1 (p = 0.004), 17:0 (p = 0.01), 18:1 (p = 0.0002), 18:2 (p = 0.002), and 20:3 (p = 0.0007), but not 18:0 (p = 0.07), 20:4 (p = 0.09) compared with those in the lower three quartiles in multivariable linear regression models adjusting for age, sex, and height. Multiple machine‐learning algorithms showed an area under the receiver operating characteristic curve of 0.638 (95% confidence interval, 0.554, 0.723) comparing six LPC in adults in the lower three quartiles of kPCr with the highest quartile. Low plasma LPC are associated with impaired mitochondrial oxidative capacity in adults.

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“…Once the lipid film was dried, an electroformation chamber was assembled as described (72). GUVs and GMVs were constructed by electroformation at room temperature as previously described (26,72,73). Once electroformation was complete, vesicles were extracted from the chamber using a 20 1 ⁄ 2-gauge needle/syringe and allowed to equilibrate briefly prior to microscopy sample preparation.…”

Section: Construction Of Guvs and Gmvsmentioning

confidence: 99%

“…There are several major gaps in knowledge regarding CLenriched domain organization. The first major limitation is that many studies have not effectively modeled the inner mitochondrial composition and even relied on lipid raft models (24,26). Approximately 70% of the inner mitochondrial membrane is accounted for by phosphatidylcholine (40%) and phosphatidylethanolamine (30%), whereas CL makes up about 15-20% of total phospholipids (7).…”

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confidence: 99%

Proteolipid domains form in biomimetic and cardiac mitochondrial vesicles and are regulated by cardiolipin concentration but not monolyso-cardiolipin

Pennington

Sullivan

Fix

et al. 2018

Journal of Biological Chemistry

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Cardiolipin (CL) is an anionic phospholipid mainly located in the inner mitochondrial membrane, where it helps regulate bioenergetics, membrane structure, and apoptosis. Localized, phase-segregated domains of CL are hypothesized to control mitochondrial inner membrane organization. However, the existence and underlying mechanisms regulating these mitochondrial domains are unclear. Here, we first isolated detergent-resistant cardiac mitochondrial membranes that have been reported to be CL-enriched domains. Experiments with different detergents yielded only nonspecific solubilization of mitochondrial phospholipids, suggesting that CL domains are not recoverable with detergents. Next, domain formation was investigated in biomimetic giant unilamellar vesicles (GUVs) and newly synthesized giant mitochondrial vesicles (GMVs) from mouse hearts. Confocal fluorescent imaging revealed that introduction of cytochrome into membranes promotes macroscopic proteolipid domain formation associated with membrane morphological changes in both GUVs and GMVs. Domain organization was also investigated after lowering tetralinoleoyl-CL concentration and substitution with monolyso-CL, two common modifications observed in cardiac pathologies. Loss of tetralinoleoyl-CL decreased proteolipid domain formation in GUVs, because of a favorable Gibbs-free energy of lipid mixing, whereas addition of monolyso-CL had no effect on lipid mixing. Moreover, murine GMVs generated from cardiac acyl-CoA synthetase-1 knockouts, which have remodeled CL acyl chains, did not perturb proteolipid domains. Finally, lowering the tetralinoleoyl-CL content had a stronger influence on the oxidation status of cytochrome than did incorporation of monolyso-CL. These results indicate that proteolipid domain formation in the cardiac mitochondrial inner membrane depends on tetralinoleoyl-CL concentration, driven by underlying lipid-mixing properties, but not the presence of monolyso-CL.

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Distinct membrane properties are differentially influenced by cardiolipin content and acyl chain composition in biomimetic membranes

Cited by 31 publications

References 85 publications

Murine diet-induced obesity remodels cardiac and liver mitochondrial phospholipid acyl chains with differential effects on respiratory enzyme activity

Murine diet-induced obesity remodels cardiac and liver mitochondrial phospholipid acyl chains with differential effects on respiratory enzyme activity

Low plasma lysophosphatidylcholines are associated with impaired mitochondrial oxidative capacity in adults in the Baltimore Longitudinal Study of Aging

Proteolipid domains form in biomimetic and cardiac mitochondrial vesicles and are regulated by cardiolipin concentration but not monolyso-cardiolipin

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