Summary of project PR002686
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 PR002686. The data can be accessed directly via it's Project DOI: 10.21228/M8FZ77 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002686 |
| Project DOI: | doi: 10.21228/M8FZ77 |
| Project Title: | Mitochondria-localized MLKL channel function drives proinflammatory response independent of necroptosis |
| Project Summary: | Mixed lineage kinase domain-like protein (MLKL) has been well-established as an executor of necroptosis. However, its necroptosis independent functions have recently garnered attention, particularly its involvement in non-necroptotic pathological processes. Here, we found that MLKL expression was upregulated in macrophages during inflammation. Our proteomic and functional assays revealed that, despite the absence of necroptosis, metabolic dysregulation and inflammatory responses were still MLKL-dependent. These phenomena were notably suppressed in MLKL-deficient macrophages. Further investigation showed that MLKL translocates to the mitochondrial membrane during inflammation, where its interaction with cardiolipin enhances channel activity, resulting in mitochondrial dysfunction and an amplified inflammatory response. In both in vitro and in vivo models, MLKL deficiency restored mitochondrial function, relieved inflammation, reduced tissue damage. These findings establish MLKL channel as a crucial regulator of macrophage inflammation, independent of its role in necroptosis, and highlight its potential as a therapeutic target in inflammation-associated diseases such as sepsis. |
| Institute: | Fudan University |
| Department: | Institutes of Biomedical Sciences |
| Laboratory: | Systems biology Laboratory |
| Last Name: | Qie |
| First Name: | Jingbo |
| Address: | Institutes of Biomedical Sciences, Fudan University, No. 131, Dong 'an Road, Shanghai 200032, China |
| Email: | jingboqie@fudan.edu.cn |
| Phone: | 17717890408 |
Summary of all studies in project PR002686
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004258 | Mitochondria-localized MLKL channel function drives proinflammatory response independent of necroptosis | Mus musculus | Fudan University | MS | 2025-10-10 | 1 | 48 | Uploaded data (279.5M)* |
