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:. Inserm-umr-s-769, L. Labex, and F. Châtenay-malabry, , vol.2

, Buffer H+ Bovine serum albumin (BSA): weigh 102

, Mitochondria membrane potential and swelling

, Buffer S: weigh 68.46g sucrose, 2.09g 3-(N-morpholino)propanesulfonic acid (MOPS), 3.8mg EGTA

, Succinate stock solution: weigh 1.35g succinate; buffer: 250mM sucrose, 15mM Potassium chloride (KCl), p.1

, EGTA, 5mM Magnesium chloride (MgCl2), p.30

, Reconstitute Mito-ID® Extracellular O 2 Sensor kit

, Loading buffer (5×): Tris 300mM, Glycerol 50%, sodium dodecylsulfate (SDS)

, 5%, dithiothreitol (DTT) 50mM

, -15% precast gel (BioRad Mini-PROTEAN TGX)

, Migration buffer (10×): weigh 30g Tris Base, p.144

, DTT (10×)

. Membrane,

, Trans-blot Turbo transfer system

, Phosphate buffered saline (PBS)-Tween (10×)

, Antibody anti-cytochrome c (BD Pharmingen)

, Ultra-sensitive enhanced chemiluminescent (ECL) substrate, e.g. Supersignal West Femto Maximum Sensitivity Substrate

, Gel imaging system, e.g. Chemidoc (BioRad), p.169

, Block the membrane with 5% of milk in PBS-Tween

, Wash the membrane with PBS-Tween for 6×5min

, Wash the membrane with PBS-Tween for 6×5min

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C. Martel, M. Allouche, D. D. Esposti, E. Fanelli, C. Boursier et al.,

, 71 5. VDAC phosphorylation in lipid-induced liver pathology, VDAC, its post-translational modifications and their implication

.. .. Acknowledgments,

.. .. References, 74 1. Introduction The existence of channels in the mitochondrial outer membrane (OM) has been evidenced concomitantly by electrophysiology and electron microscopy in the, 1970.

. Shinohara, isoforms, i.e. VDAC1, 2, and 3 in mammals (Colombini and Mannella, 2000.

, Abbreviations: ACSL, long-chain acyl-CoA synthetase

, ANT, adenine nucleotide translocase; BN-PAGE, blue-native polyacrylamide gel electrophoresis

, CL, cardiolipin; CPT1a, carnitine palmitoyltransferase 1a

. Cypd,

. Ko,

I. Im and . Membrane,

L. Lpc,

. Lpe,

. Pc, ;. Pg, and . Ptp,

. Tnf-?,

, E-mail address: catherine, VDAC, voltage-dependent anion channel. ? Corresponding author at: INSERM UMR-S 769


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C. Martel, / Mitochondrion, vol.19, pp.69-77, 2014.

. Inserm-u848, G. Institut, and . Roussy, Université Paris-Sud 11, PR1, 39 rue Camille Desmoulins

. Inserm-u-996,

, Metabolomics Platform, Institut Gustave Roussy

, Keywords: apoptosis; chemotherapy

, DTT, dithiothreitol; IRE1, ER to nucleus signaling 1; MMP, mitochondrial membrane permeabilization

, MS, mass spectrometry; NSLC, non-small lung cancer

, PDI, protein disulfide isomerase; PERK, protein kinase RNA-like endoplasmic reticulum kinase; GRP78, 78 kDa glucose-regulated protein

. Dcm, Cell Death and Differentiation, vol.21, pp.685-695, 2014.

M. Promega and . Wi, ) with the following parameters: Swiss-Prot 57.7 database, Homo sapiens taxonomy, one missed cleavage by trypsin, fixed carbamido-SDS-PAGE and immunoblotted with the following antibodies: ATF6 (Abcam, & 2014 Macmillan Publishers Limited All rights reserved 1350-9047/14 trypsin

. Bax, BD Biosciences

, Caspase, vol.9

, Cell Signaling, p.78

, HSP70

, Abcam, p.1

, Abcam, p.3

S. Pdia4-(abcam and . Cruz,

, Santa Cruz and Abcam, p.6

, PERK (Abcam); and RIPK1 (BioVision)

, Cell viability analysis. The number of surviving cells was determined by the WST-1 assay

, Cell death analysis. A549 and A2780 WT and resistant cells were analyzed for cell death as previously described

. Briefly, . Tmrm, S. Invitrogen, and . Aubin, France) flow cytometry (FACSCalibur flow cytometer, BD Biosciences). Finally, early and late apoptosis were analyzed using Annexin-PE/ 7AAD (BD Pharmingen

(. Assay and . Promega,

, Villeurbanne, France) by using insulin as substrate to evaluate PDI activity in A549 whole extracts and ER fraction. Clonogenic assay. Cells were harvested, washed with PBS and plated for 2-3 weeks at 37 1C. Then, colonies were stained with 0.25% of crystal violet and counted using GS800 calibrated densitometer (Bio-Rad) and PDQuest software (Bio-Rad). [Ca 2 þ ] measurements in the ER and cytoplasm. For steady state, PDI activity assay. ProteoStat PDI assay kit was used following the manufacturer's instruction

, fitted with a computer-controlled motorized heated stage (37 1C, Applied Scientific Instrumentation, with a  40 Hamamatsu C10600-10B CCD camera, vol.3, p.substrate

, la Recherche Médicale (FRM

, Institut National du Cancer

L. Labex,

, LabEx Immuno-Oncologie

, Fondation de France

, Fondation Bettencourt-Schueller

, AXA Chair for Longevity Research; and Cancéropôle Ile-de-France and Paris Alliance of Cancer Research Institutes (PACRI)

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