Summary of project PR001817
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 PR001817. The data can be accessed directly via it's Project DOI: 10.21228/M8V72T This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001817 |
| Project DOI: | doi: 10.21228/M8V72T |
| Project Title: | A mitophagy sensor PPTC7 integrates homeostatic and physiological signals to regulate mitophagy and mitochondrial mass |
| Project Summary: | Mitophagy mediated by receptors BNIP3 and NIX critically regulates mitochondrial mass under developmental and pathophysiological conditions. Cellular BNIP3 and NIX levels are tightly controlled by SCFFBXL4-mediated ubiquitination to prevent excessive mitophagy and lethal disease. Here we report that knockout of PPTC7, a mitochondrial matrix protein, hyperactivates BNIP3/NIX-mediated mitophagy in vitro and in vivo. Biochemically, the PPTC7 precursor is trapped by BNIP3 and NIX to mitochondrial outer-membrane, where PPTC7 scaffolds the assembly of the substrate-PPTC7-SCFFBXL4 holocomplex to degrade BNIP3 and NIX, forming a homeostatic regulatory loop. PPTC7 possesses an unusually weak mitochondrial targeting sequence to facilitate its outer-membrane retention and mitophagy control. Upon starvation, PPTC7 is transcriptionally upregulated in mouse liver to repress mitophagy, which critically maintains hepatic mitochondrial mass, bioenergetics and gluconeogenesis. Collectively, PPTC7 functions as a mitophagy sensor that integrates homeostatic and physiological signals to dynamically control BNIP3 and NIX degradation, thereby maintaining proper mitochondrial mass and cellular homeostasis. |
| Institute: | National Institute of Biological Sciences,Beijing |
| Last Name: | Ma |
| First Name: | Yan |
| Address: | Zhongguancun Life Science Park |
| Email: | mayan@nibs.ac.cn |
| Phone: | +86-01080726688 |
Summary of all studies in project PR001817
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002925 | Metabolite analysis of hepatic Pptc7-ko mice under fed or fasting conditions | Mus musculus | National Institute of Biological Sciences, Beijing | MS | 2023-10-26 | 1 | 19 | Uploaded data (824.1M)* |
