Surface-Binding to Cardiolipin Nanodomains Triggers Cytochrome c Pro-apoptotic Peroxidase Activity via Localized Dynamics

Mingyue Li; Abhishek Mandal; Vladimir A. Tyurin; Maria DeLucia; Jinwoo Ahn; Valerian E. Kagan; Patrick C. A. van der Wel

doi:10.1016/j.str.2019.02.007

Surface-Binding to Cardiolipin Nanodomains Triggers Cytochrome c Pro-apoptotic Peroxidase Activity via Localized Dynamics

Mingyue Li, Abhishek Mandal, Vladimir A. Tyurin, Maria DeLucia, Jinwoo Ahn, Valerian E. Kagan, Patrick C. A. van der Wel^*

^*Corresponding author for this work

Solid State Nuclear Magnetic Resonance

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Abstract

The peroxidation of cardiolipins by reactive oxygen species, which is regulated and enhanced by cytochrome c (cyt c), is a critical signaling event in mitochondrial apoptosis. We probe the molecular underpinnings of this mitochondrial death signal through structural and functional studies of horse heart cyt c binding to mixed-lipid membranes containing cardiolipin with mono- and polyunsaturated acyl chains. Lipidomics reveal the selective oxidation of polyunsaturated fatty acid (PUFA) cardiolipin (CL), while multidimensional solid-state NMR probes the structure and dynamics of the membrane and the peripherally bound protein. The hydrophilic milieu at the membrane interface stabilizes a native-like fold, but also leads to localized flexibility at the membrane-interacting protein face. PUFA CL acts as both a preferred substrate and a dynamic regulator by affecting the dynamics of the cyt c N70-I85 Ω loop, which covers the heme cavity.

Original language	English
Pages (from-to)	806-815.e4
Number of pages	15
Journal	Structure
Volume	27
Issue number	5
Early online date	14-Mar-2019
DOIs	https://doi.org/10.1016/j.str.2019.02.007
Publication status	Published - 7-May-2019

Keywords

cytochrome
cardiolipin
mitochondrial protein
apoptosis
membrane protein
PUFA
protein structure and dynamics
membrane oxidation
lipidomics
solid-state NMR
FERRICYTOCHROME-C
NATIVE-LIKE
NMR
MITOCHONDRIA
MEMBRANES
PROTEINS
TRANSITIONS
COEXISTENCE
INHIBITORS
RESOLUTION

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10.1016/j.str.2019.02.007Licence: Elsevier

Surface-Binding to Cardiolipin Nanodomains TriggersCytochromecPro-apoptotic Peroxidase Activityvia Localized DynamicsFinal publisher's version, 3.81 MBLicence: Taverne

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37 Citations
1 Review article

Redox phospholipidomics of enzymatically generated oxygenated phospholipids as specific signals of programmed cell death
Kagan, V. E., Tyurina, Y. Y., Sun, W. Y., Vlasova, L. L., Dar, H., Tyurin, V. A., Amoscato, A. A., Mallampalli, R., van der Wel, P. C. A., He, R. R., Shvedova, A. A., Gabrilovich, D. & Bayir, H., 1-Feb-2020, In: Free Radical Biology and Medicine. 147, p. 231-241 11 p.
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221 Downloads (Pure)

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@article{76d3ff9641644a5cb402da1b9aac5423,

title = "Surface-Binding to Cardiolipin Nanodomains Triggers Cytochrome c Pro-apoptotic Peroxidase Activity via Localized Dynamics",

abstract = "The peroxidation of cardiolipins by reactive oxygen species, which is regulated and enhanced by cytochrome c (cyt c), is a critical signaling event in mitochondrial apoptosis. We probe the molecular underpinnings of this mitochondrial death signal through structural and functional studies of horse heart cyt c binding to mixed-lipid membranes containing cardiolipin with mono- and polyunsaturated acyl chains. Lipidomics reveal the selective oxidation of polyunsaturated fatty acid (PUFA) cardiolipin (CL), while multidimensional solid-state NMR probes the structure and dynamics of the membrane and the peripherally bound protein. The hydrophilic milieu at the membrane interface stabilizes a native-like fold, but also leads to localized flexibility at the membrane-interacting protein face. PUFA CL acts as both a preferred substrate and a dynamic regulator by affecting the dynamics of the cyt c N70-I85 Ω loop, which covers the heme cavity.",

keywords = "cytochrome, cardiolipin, mitochondrial protein, apoptosis, membrane protein, PUFA, protein structure and dynamics, membrane oxidation, lipidomics, solid-state NMR, FERRICYTOCHROME-C, NATIVE-LIKE, NMR, MITOCHONDRIA, MEMBRANES, PROTEINS, TRANSITIONS, COEXISTENCE, INHIBITORS, RESOLUTION",

author = "Mingyue Li and Abhishek Mandal and Tyurin, \{Vladimir A.\} and Maria DeLucia and Jinwoo Ahn and Kagan, \{Valerian E.\} and \{van der Wel\}, \{Patrick C. A.\}",

year = "2019",

month = may,

day = "7",

doi = "10.1016/j.str.2019.02.007",

language = "English",

volume = "27",

pages = "806--815.e4",

journal = "Structure",

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T1 - Surface-Binding to Cardiolipin Nanodomains Triggers Cytochrome c Pro-apoptotic Peroxidase Activity via Localized Dynamics

AU - Li, Mingyue

AU - Mandal, Abhishek

AU - Tyurin, Vladimir A.

AU - DeLucia, Maria

AU - Ahn, Jinwoo

AU - Kagan, Valerian E.

AU - van der Wel, Patrick C. A.

PY - 2019/5/7

Y1 - 2019/5/7

N2 - The peroxidation of cardiolipins by reactive oxygen species, which is regulated and enhanced by cytochrome c (cyt c), is a critical signaling event in mitochondrial apoptosis. We probe the molecular underpinnings of this mitochondrial death signal through structural and functional studies of horse heart cyt c binding to mixed-lipid membranes containing cardiolipin with mono- and polyunsaturated acyl chains. Lipidomics reveal the selective oxidation of polyunsaturated fatty acid (PUFA) cardiolipin (CL), while multidimensional solid-state NMR probes the structure and dynamics of the membrane and the peripherally bound protein. The hydrophilic milieu at the membrane interface stabilizes a native-like fold, but also leads to localized flexibility at the membrane-interacting protein face. PUFA CL acts as both a preferred substrate and a dynamic regulator by affecting the dynamics of the cyt c N70-I85 Ω loop, which covers the heme cavity.

AB - The peroxidation of cardiolipins by reactive oxygen species, which is regulated and enhanced by cytochrome c (cyt c), is a critical signaling event in mitochondrial apoptosis. We probe the molecular underpinnings of this mitochondrial death signal through structural and functional studies of horse heart cyt c binding to mixed-lipid membranes containing cardiolipin with mono- and polyunsaturated acyl chains. Lipidomics reveal the selective oxidation of polyunsaturated fatty acid (PUFA) cardiolipin (CL), while multidimensional solid-state NMR probes the structure and dynamics of the membrane and the peripherally bound protein. The hydrophilic milieu at the membrane interface stabilizes a native-like fold, but also leads to localized flexibility at the membrane-interacting protein face. PUFA CL acts as both a preferred substrate and a dynamic regulator by affecting the dynamics of the cyt c N70-I85 Ω loop, which covers the heme cavity.

KW - cytochrome

KW - cardiolipin

KW - mitochondrial protein

KW - apoptosis

KW - membrane protein

KW - PUFA

KW - protein structure and dynamics

KW - membrane oxidation

KW - lipidomics

KW - solid-state NMR

KW - FERRICYTOCHROME-C

KW - NATIVE-LIKE

KW - NMR

KW - MITOCHONDRIA

KW - MEMBRANES

KW - PROTEINS

KW - TRANSITIONS

KW - COEXISTENCE

KW - INHIBITORS

KW - RESOLUTION

U2 - 10.1016/j.str.2019.02.007

DO - 10.1016/j.str.2019.02.007

M3 - Article

SN - 0969-2126

VL - 27

SP - 806-815.e4

JO - Structure

JF - Structure

IS - 5

ER -

Surface-Binding to Cardiolipin Nanodomains Triggers Cytochrome c Pro-apoptotic Peroxidase Activity via Localized Dynamics

Abstract

Keywords

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Research output

Redox phospholipidomics of enzymatically generated oxygenated phospholipids as specific signals of programmed cell death

Cite this