Summary of project PR001988
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 PR001988. The data can be accessed directly via it's Project DOI: 10.21228/M8RJ07 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001988 |
| Project DOI: | doi: 10.21228/M8RJ07 |
| Project Title: | Rhodoquinone is an Electron Carrier in the Mammalian Electron Transport Chain |
| Project Summary: | Ubiquinone (UQ), the only known electron carrier in the mammalian electron transport chain (ETC), delivers electrons to both oxygen (O2) and fumarate as terminal electron acceptors. As fumarate has a lower reduction potential than UQ, fumarate reduction is only thermodynamically favorable when ubiquinol, the reduced form of UQ, accumulates. Paradoxically, some tissues reduce fumarate without ubiquinol buildup, suggesting another mechanism enables fumarate reduction in mammals. Here, we identify rhodoquinone (RQ), a novel mammalian electron carrier that directs electrons to fumarate, instead of O2, as the favored terminal electron acceptor. RQ, which is undetectable in cultured mammalian cells, is enriched in tissues that catalyze fumarate reduction. RQ and UQ-directed ETC circuits support distinct programs of mitochondrial function. Through expression of a bacterial enzyme that converts UQ into RQ and development a novel RQ analog, we demonstrate that reprogramming the mammalian ETC from the UQ to RQ circuit renders cells highly resistant to hypoxia exposure. Thus, we establish RQ as a fundamental component of the mammalian ETC and unveil reprogramming the ETC to the RQ-circuit as a tractable strategy to treat hypoxia-related diseases. |
| Institute: | UMass Chan Medical School |
| Department: | Program in Molecular Medicine |
| Laboratory: | Spinelli Lab |
| Last Name: | UMass Chan |
| First Name: | Spinelli Lab |
| Address: | 55 Lake Avenue North, Worcester, Massachusetts, 01605, USA |
| Email: | spinellilab@gmail.com |
| Phone: | (508) 856-8989 ext. 68148 |
Summary of all studies in project PR001988
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003192 | Aspartate tracing in Wildtype and UQCRC2 Knockout 143B Cells | Homo sapiens | UMass Chan Medical School | MS | 2025-02-04 | 1 | 9 | Uploaded data (781.5M)* |
| ST003197 | UQ/RQ panel on wildtype mouse tissue | Mus musculus | UMass Chan Medical School | MS* | 2025-02-04 | 1 | 104 | Uploaded data (5G)* |
| ST003198 | UQ/RQ panel on human tissue | Homo sapiens | UMass Chan Medical School | MS* | 2025-02-04 | 1 | 48 | Uploaded data (2.2G)* |
| ST003204 | Glutamine Tracing Assay on Caki1 WT and 769P WT versus Caki1 RquA and 769P RquA | Homo sapiens | UMass Chan Medical School | MS | 2025-02-04 | 1 | 24 | Uploaded data (1.8G)* |
| ST003214 | Glutamine Tracing Assay in RquA AAV Injected Mice with a Standard Curve | Mus musculus | UMass Chan Medical School | MS | 2025-02-04 | 1 | 21 | Uploaded data (2G)* |
| ST003217 | Measuring UQ/UQH2 in WT and RquA 143B cell in Hypoxia | Homo sapiens | UMass Chan Medical School | MS* | 2025-02-04 | 1 | 12 | Uploaded data (906.2M)* |
| ST003218 | Glutamine Tracing Assay in WT and SDHB KO 143B cells Treated with HKJS003 | Homo sapiens | UMass Chan Medical School | MS | 2025-02-04 | 1 | 18 | Uploaded data (1.8G)* |
| ST003397 | Glutamine Tracing in Mice injected with HKJS001 and Malonic Acid | Mus musculus | UMass Chan Medical School | MS | 2025-02-04 | 1 | 23 | Uploaded data (2.4G)* |
| ST003404 | Aspartate Tracing in SDHB KO RquA 143B Cells | Homo sapiens | UMass Chan Medical School | MS | 2025-02-04 | 1 | 18 | Uploaded data (2G)* |
