Summary of project PR002404
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 PR002404. The data can be accessed directly via it's Project DOI: 10.21228/M8WJ9W This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002404 |
| Project DOI: | doi: 10.21228/M8WJ9W |
| Project Title: | Hepatic Coenzyme Q (CoQ) Deficiency Drives Reverse Electron Transport and Disrupts Hepatic Metabolic Homeostasis in Obesity |
| Project Summary: | Mitochondrial reactive oxygen species (mROS) play a crucial role in physiology. While excessive mROS production has been associated with several disease states, its precise sources, regulation, and mechanisms of generation in vivo remain unclear, limiting translational efforts. mROS production is not a single process; at least 11 distinct sites associated with the electron transport chain and matrix substrate oxidation can partially reduce oxygen to superoxide and hydrogen peroxide. These sites exhibit substrate specificity and differ in their capacities to generate mROS. Here, we show that in obesity, hepatic coenzyme Q (CoQ) synthesis in vivo is impaired, leading to decreased CoQ9 levels and an increased CoQH₂/CoQ ratio. These alterations in CoQ metabolism drive excessive mROS production via reverse electron transport (RET) at site IQ of complex I. Using multiple complementary genetic and pharmacological in vivo models, we demonstrate that RET is critical for maintaining metabolic health. Furthermore, we show that in patients with steatosis, hepatic CoQ biosynthesis is also suppressed, and the CoQH₂/CoQ ratio positively correlates with steatosis grade. Our data identify a highly selective mechanism of pathological mROS production in obesity, which can be targeted to preserve metabolic homeostasis. |
| Institute: | Harvard School of Public Health |
| Department: | Molecular Metabolism |
| Laboratory: | Hotamisligil Lab |
| Last Name: | de Lima Sales Goncalves |
| First Name: | Renata |
| Address: | 665 Huntington Ave bld 1, room 609, Boston, MA, 02115, USA |
| Email: | rgoncal@hsph.harvard.edu |
| Phone: | 4159402482 |
Summary of all studies in project PR002404
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003846 | Hepatic Coenzyme Q (CoQ) Deficiency Drives Reverse Electron Transport and Disrupts Hepatic Metabolic Homeostasis in Obesity | Mus musculus | Harvard School of Public Health | MS | 2025-04-25 | 1 | 36 | Uploaded data (861.4M)* |
