Nature - USA (2020-01-02)

2

nature research | reporting summary

October 2018

study are available from the corresponding author upon reasonable request.

Field-specific reporting

Please select the one below that is the best fit for your research. If you are not sure, read the appropriate sections before making your selection.

Life sciences Behavioural & social sciences Ecological, evolutionary & environmental sciences

For a reference copy of the document with all sections, see nature.com/documents/nr-reporting-summary-flat.pdf

Life sciences study design

All studies must disclose on these points even when the disclosure is negative.

Sample size No statistical methods were used to predetermine the sample sizes.

Data exclusions No data was excluded from analysis.

Replication In Fig. 2d, Fig. 4g, Extended Data Fig. 4g, Extended Data Fig. 5j and Extended Data Fig. 6g, RNA sequencing analysis of each sample was

performed in duplicate. In Fig. 2b, c, Extended Data Fig. 2d-g, Extended Data Fig. 3a, b, Extended Data Fig. 4h, Single cell RNA sequencing

analysis of patient sample was performed in duplicate and healthy control (C1) was performed once. In Fig. 3d and Extended Data Fig. 4d,

NanoString analysis of patient and healthy controls PBMCs were performed once. In Fig. 4i, the immunofluorescence of cytosolic ROS (green

foci) in fibroblasts was performed in duplicate. The other data are representative of three independent biological replicates.

Randomization Multiple age and gender matched healthy controls used in the experiment were randomly selected. Patient samples were taken multiple

times and used for independent biological replicate experiments.

Blinding Blinding was not possible as the authors who performed the experiment also analyzed the data.

Reporting for specific materials, systems and methods

We require information from authors about some types of materials, experimental systems and methods used in many studies. Here, indicate whether each material,

system or method listed is relevant to your study. If you are not sure if a list item applies to your research, read the appropriate section before selecting a response.

Materials & experimental systems

n/a Involved in the study

Antibodies

Eukaryotic cell lines

Palaeontology

Animals and other organisms

Human research participants

Clinical data

Methods

n/a Involved in the study

ChIP-seq

Flow cytometry

MRI-based neuroimaging

Antibodies

Antibodies used Western Blot:

β-Actin (Cell Signaling Technology, 4970, clone 13E5, lot 15, 1:1000), β-Tubulin (Cell Signaling Technology, 86298, clone D3U1W,

lot 1, 1:1000), GAPDH (Cell Signaling Technology, 5174, clone D16H11, lot 6, 1:1000), RIPK1 (Cell Signaling Technology, 3493,

clone D94C12, lot 3, 1:1000), p-RIPK1 (Ser166) (Cell Signaling Technology, 65746, clone D1L3S, lot 02, 1:1000), MLKL (Cell

Signaling Technology, 14993, clone D2I6N, lot 3, 1:1000), p-MLKL (Ser358) (Cell Signaling Technology, 91689, clone D6H3V, lot 3,

1:1000), p-MLKL (Ser345) (Cell Signaling Technology, 37333, clone D6E3G, lot 2, 1:1000), p65 (Cell Signaling Technology, 8242,

clone D14E12, lot 9, 1:1000), p-p65 (Ser65) (Cell Signaling Technology, 3033, clone 93H1, lot 16, 1:1000), IKKα (Cell Signaling

Technology, 11930, clone 3G12, lot 5, 1:1000), IKKβ (Cell Signaling Technology, 2370, clone D30C6, lot 4, 1:1000), p-IKKα/β

(Ser176/180) (Cell Signaling Technology, 2697, clone 16A6, lot 19, 1:1000), IκBα (Cell Signaling Technology, 4814, clone L35A5,

lot 17, 1:1000), p-IκBα (Ser32) (Cell Signaling Technology, 2859, clone 14D4, lot 18, 1:1000), p38 (Cell Signaling Technology,

8690, clone D13E1, lot 6, 1:1000), p-p38 (Thr180/Tyr182) (Cell Signaling Technology, 4511, clone D3F9, lot 13, 1:1000), TNFR1

(Cell Signaling Technology, 3736, clone C25C1, lot 2, 1:1000), caspase-8 (Cell Signaling Technology, 4790, clone D35G2, lot 2,

1:1000), cl-caspase-8 (Cell Signaling Technology, 8592, clone D5B2, lot 2, 1:1000), caspase-3 (Cell Signaling Technology, 9662,

polyclonal, lot 18, 1:1000), cleaved-caspase-3 (Asp175) (Cell Signaling Technology, 9661, polyclonal, lot 18, 1:1000), HA-Tag (Cell

Signaling Technology, 3724, clone C29F1, lot 8, 1:1000), SLC7A11 (Cell Signaling Technology, 12691, clone D2M7A, lot 1, 1:1000),

Cyclophilin A (Abcam, ab41684, polyclonal, lot GR3201186-1, 1:1000), GPX4 (Abcam, ab125066, clone EPNCIR144, lot

GR251529-29, 1:1000), Lamp-2A (Abcam, ab125068, clone EPR4207(2), lot GR7472-1, 1:1000), COX2 (Abcam, ab15191,

polyclonal, 1:1000), p53 (Abcam, ab32389, clone E26, 1:1000), FADD (Santa Cruz Biotechnology, sc-6036, clone M-19, 1:1000),

ACSL4 (Santa Cruz Biotechnology, sc-365230, clone F-4, lot G1116, 1:1000), HSC70 (Proteintech Group, 10654-1-AP, polyclonal,

1:1000), HSP90 (Affinity, BF9107, clone AFB5588, lot 55e0886, 1:1000), p-RIPK1 (Ser166) (Biolynx, BX60008, clone YJY-1-5,