Summary of Study ST002738
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001703. The data can be accessed directly via it's Project DOI: 10.21228/M8K99P This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002738 |
| Study Title | Innate immune and metabolic signaling retain damaged mitochondria at cell membranes for mitoxyperilysis |
| Study Summary | Innate immune activation coupled with metabolic disruptions play critical roles in many diseases, often leading to mitochondrial dysfunction and oxidative stress that drive pathogenesis. However, mechanistic regulation under these conditions remains poorly defined. Here, we report a distinct lytic cell death mechanism induced by innate immune signaling and metabolic disruption, independent of caspase activity and previously described pyroptosis, PANoptosis, necroptosis, ferroptosis, and oxeiptosis. Instead, mitochondria undergoing BAX/BAK1/BID-dependent oxidative stress maintained prolonged plasma membrane contact, leading to local oxidative damage, a process we termed mitoxyperiosis. This process then caused membrane lysis and cell death, mitoxyperilysis. mTORC2 regulated the cell death, and mTOR inhibition restored cytoskeletal activity for lamellipodia retractions to mobilize mitochondria away from the membrane, preserving integrity. Activating this pathway in vivo regressed tumors in an mTORC2-dependent manner. Overall, our results identify a lytic cell death modality in response to the synergism of innate immune signaling and metabolic disruption. |
| Institute | St Jude Children's Research Hospital |
| Last Name | Wang |
| First Name | Yaqiu |
| Address | 262 Danny Thomas Pl |
| yaqiu.wang@stjude.org | |
| Phone | 901-595--3477 |
| Submit Date | 2023-06-16 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzXML |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-11-28 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR001703 |
| Project DOI: | doi: 10.21228/M8K99P |
| Project Title: | Innate immune and metabolic signaling retain damaged mitochondria at cell membranes for mitoxyperilysis |
| Project Summary: | Innate immune activation coupled with metabolic disruptions play critical roles in many diseases, often leading to mitochondrial dysfunction and oxidative stress that drive pathogenesis. However, mechanistic regulation under these conditions remains poorly defined. Here, we report a distinct lytic cell death mechanism induced by innate immune signaling and metabolic disruption, independent of caspase activity and previously described pyroptosis, PANoptosis, necroptosis, ferroptosis, and oxeiptosis. Instead, mitochondria undergoing BAX/BAK1/BID-dependent oxidative stress maintained prolonged plasma membrane contact, leading to local oxidative damage, a process we termed mitoxyperiosis. This process then caused membrane lysis and cell death, mitoxyperilysis. mTORC2 regulated the cell death, and mTOR inhibition restored cytoskeletal activity for lamellipodia retractions to mobilize mitochondria away from the membrane, preserving integrity. Activating this pathway in vivo regressed tumors in an mTORC2-dependent manner. Overall, our results identify a lytic cell death modality in response to the synergism of innate immune signaling and metabolic disruption. |
| Institute: | St Jude Children's Research Hospital |
| Last Name: | Wang |
| First Name: | Yaqiu |
| Address: | 262 Danny Thomas Pl, Memphis, Tennessee, 38105, USA |
| Email: | yaqiu.wang@stjude.org |
| Phone: | +1-901-595-3477 |
Subject:
| Subject ID: | SU002845 |
| Subject Type: | Cultured cells |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Species Group: | Mammals |
Factors:
Subject type: Cultured cells; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Treatment |
|---|---|---|
| SA288762 | YW_01272023_Metabo_00_Neg | BLANK |
| SA288763 | YW_01272023_Metabo_00_Pos | BLANK |
| SA288764 | YW_01272023_Metabo_10_Neg | CS+LPS_WT |
| SA288765 | YW_01272023_Metabo_11_Neg | CS+LPS_WT |
| SA288766 | YW_01272023_Metabo_10_Pos | CS+LPS_WT |
| SA288767 | YW_01272023_Metabo_11_Pos | CS+LPS_WT |
| SA288768 | YW_01272023_Metabo_12_Pos | CS+LPS_WT |
| SA288769 | YW_01272023_Metabo_12_Neg | CS+LPS_WT |
| SA288770 | YW_01272023_Metabo_07_Neg | CS_WT |
| SA288771 | YW_01272023_Metabo_08_Neg | CS_WT |
| SA288772 | YW_01272023_Metabo_09_Neg | CS_WT |
| SA288773 | YW_01272023_Metabo_07_Pos | CS_WT |
| SA288774 | YW_01272023_Metabo_09_Pos | CS_WT |
| SA288775 | YW_01272023_Metabo_08_Pos | CS_WT |
| SA288776 | YW_01272023_Metabo_06_Pos | LPS_WT |
| SA288777 | YW_01272023_Metabo_06_Neg | LPS_WT |
| SA288778 | YW_01272023_Metabo_04_Neg | LPS_WT |
| SA288779 | YW_01272023_Metabo_04_Pos | LPS_WT |
| SA288780 | YW_01272023_Metabo_05_Neg | LPS_WT |
| SA288781 | YW_01272023_Metabo_05_Pos | LPS_WT |
| SA288782 | YW_01272023_Metabo_01_Pos | Media_WT |
| SA288783 | YW_01272023_Metabo_01_Neg | Media_WT |
| SA288784 | YW_01272023_Metabo_02_Neg | Media_WT |
| SA288785 | YW_01272023_Metabo_03_Pos | Media_WT |
| SA288786 | YW_01272023_Metabo_03_Neg | Media_WT |
| SA288787 | YW_01272023_Metabo_02_Pos | Media_WT |
| Showing results 1 to 26 of 26 |
Collection:
| Collection ID: | CO002838 |
| Collection Summary: | Ten million BMDMs were stimulated as indicated in 100 mm plates for 9 h. The medium was removed by aspiration, and the cells were washed once with ice-cold saline. Next, the cells were carefully harvested using a plastic scraper in 1.5 ml ice-cold saline. The cells were centrifuged at 150 × g for 2 min at room temperature, and the cell pellets were flash-frozen in liquid nitrogen and then stored at −80°C for a later extraction of metabolites. |
| Sample Type: | Cultured cells |
| Storage Conditions: | -80℃ |
Treatment:
| Treatment ID: | TR002854 |
| Treatment Summary: | Treatment of cells were done as indicated in the study design table. Four types of treatment were used in WT cells. "Media_WT", "LPS_WT", "CS_WT", "CS+LPS_WT" denote the WT cells receiving Media, LPS(lipopolysaccharide), CS(starvation) and CS+LPS treatment, respectively. |
Sample Preparation:
| Sampleprep ID: | SP002851 |
| Sampleprep Summary: | Extraction of hydrophilic metabolites To extract the molecules with different polarity, an adapted three-phase solvent system was utilized to obtain total hydrophilic metabolites and lipids78. Briefly, the cell pellets were resuspended with 150 µL of saline, then 1.2 mL of chloroform/methanol/water (3:4:1, v/v/v) was added and homogenized using a Bead Ruptor Elite (OMNI international) for 30 s at 8 m/s. The homogenate was allowed to rest at 4ºC for 30 s and then centrifuged for 10 min at 21,000 g at 4ºC. After centrifugation, the upper aqueous phase was transferred into a new tube, frozen on dry ice, and then lyophilized. The dried extracts containing hydrophilic metabolites were dissolved using 40 µL of water: acetonitrile (95:5, v/v) supplemented with 10 mM ammonium acetate, then transferred into autosampler vials, and 4 µL per injection was analyzed by LC-MS. |
Chromatography:
| Chromatography ID: | CH003336 |
| Chromatography Summary: | A Vanquish Horizon UHPLC (Thermo Fisher Scientific) was used for the LC separations, using stepped gradient conditions as follows: 0–16.5 min, 1 to 50% B; 16.5–18 min, 50 to 99% B; 18–36 min, 99% B; 36–39 min, 99 to 1% B; 39–45 min, 1% B. Mobile phase A was water supplemented with 10 mM ammonium acetate. Mobile phase B was acetonitrile. The column used was an xBride BEH Amide Column (2.1 mm x 150 mm, 2.5 μm) (Waters Corp.), operated at 40°C. The flow rate was 100 μL/min, and the injection volume was 4 μL. The collected positive and negative mode data were analyzed separately. |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Waters XBridge BEH Amide (150 x 2.1mm, 2.5um) |
| Column Temperature: | 40 |
| Flow Gradient: | 0–16.5 min, 1 to 50% B; 16.5–18 min, 50 to 99% B; 18–36 min, 99% B; 36–39 min, 99 to 1% B; 39–45 min, 1% B. |
| Flow Rate: | 100 μL/min |
| Solvent A: | water supplemented with 10 mM ammonium acetate |
| Solvent B: | acetonitrile |
| Chromatography Type: | HILIC |
Analysis:
| Analysis ID: | AN004440 |
| Analysis Type: | MS |
| Chromatography ID: | CH003336 |
| Has Mz: | 1 |
| Has Rt: | 1 |
| Rt Units: | Minutes |
| Results File: | ST002738_AN004440_Results.txt |
| Units: | area |
| Analysis ID: | AN004441 |
| Analysis Type: | MS |
| Chromatography ID: | CH003336 |
| Has Mz: | 1 |
| Has Rt: | 1 |
| Rt Units: | Minutes |
| Results File: | ST002738_AN004441_Results.txt |
| Units: | area |
