Summary of Study ST002925
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
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 | ST002925 |
| Study Title | Metabolite analysis of hepatic Pptc7-ko mice under fed or fasting conditions |
| Study Summary | Hepatic Pptc7 knockout leads to mitochondrial loss under fed conditions in adult mice, which is exacerbated upon fasting. Under fasting conditions, WT liver upregulates Pptc7 levels to repress mitophagy and maintain mitochondrial mass. However, Pptc7-KO liver accumulated higher levels of Bnip3, resulting in mitophagy activation and further mitochondrial loss. To explore the metabolic changes upon Pptc7 knockout under both fed and fasting conditions, we performed a metabolite analysis of wild-type or Pptc7-KO mouse liver samples in this study. |
| Institute | National Institute of Biological Sciences, Beijing |
| Last Name | Ma |
| First Name | Yan |
| Address | Zhongguancun Life Science Park |
| mayan@nibs.ac.cn | |
| Phone | +86-01080726688 |
| Submit Date | 2023-10-11 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-10-26 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| 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 |
Subject:
| Subject ID: | SU003038 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Genotype Strain: | C57BL/6J |
| Age Or Age Range: | 10-week |
| Gender: | Male |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Genotype | Treatment |
|---|---|---|---|
| SA317872 | sample_17 | Pptc7-KO | fasting |
| SA317873 | sample_16 | Pptc7-KO | fasting |
| SA317874 | sample_14 | Pptc7-KO | fasting |
| SA317875 | sample_08 | Pptc7-KO | fasting |
| SA317876 | sample_15 | Pptc7-KO | fasting |
| SA317877 | sample_06 | Pptc7-KO | fasting |
| SA317878 | sample_19 | Pptc7-KO | fasting |
| SA317879 | sample_18 | Pptc7-KO | fasting |
| SA317880 | sample_05 | Pptc7-KO | fasting |
| SA317881 | sample_07 | Pptc7-KO | fasting |
| SA317882 | sample_13 | wild-type | fed |
| SA317883 | sample_10 | wild-type | fed |
| SA317884 | sample_03 | wild-type | fed |
| SA317885 | sample_02 | wild-type | fed |
| SA317886 | sample_04 | wild-type | fed |
| SA317887 | sample_09 | wild-type | fed |
| SA317888 | sample_11 | wild-type | fed |
| SA317889 | sample_01 | wild-type | fed |
| SA317890 | sample_12 | wild-type | fed |
| Showing results 1 to 19 of 19 |
Collection:
| Collection ID: | CO003031 |
| Collection Summary: | Mice were sacrificed and liver samples were dissected out and snap-frozen in liquid nitrogen. |
| Sample Type: | Liver |
| Storage Conditions: | -80℃ |
Treatment:
| Treatment ID: | TR003047 |
| Treatment Summary: | We performed retro-orbital injection of P28 old Pptc7-flox (GemPharmatech, T011006) mice with 1×10^12 vector genome of the empty vector or Cre AAV8 virus. 42 days post AAV injection, mice were subjected to fasting or left fed as control group respectively. Fasting was done for 18 hours from the beginning of the dark cycle at 7.p.m. to 1.p.m. next day. |
Sample Preparation:
| Sampleprep ID: | SP003044 |
| Sampleprep Summary: | Mouse livers were dissected out and snap-frozen in liquid nitrogen. Liver samples were cryo-homogenized on dry ice and 30 mg of homogenized tissue powders were weighed and extracted with 600 μL ice-cold acetonitrile/methanol/water (4/4/2) for 30 min. After centrifugation at 20,000 g for 15 min, supernatant was transferred to a new tube and dried by a Speedvac vacuum concentrator at 30°C. Dried samples were stored at -80°C and subjected to LC-MS analysis within 24 hours. |
Combined analysis:
| Analysis ID | AN004796 | AN004797 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | HILIC | HILIC |
| Chromatography system | Thermo Vanquish UHPLC | Thermo Vanquish UHPLC |
| Column | Merck ZIC-HILIC (2.1x100 mm, 3.5 μm) | Merck ZIC-HILIC (2.1x100 mm, 3.5 μm) |
| MS Type | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap |
| MS instrument name | Thermo Q Exactive HF-X Orbitrap | Thermo Q Exactive HF-X Orbitrap |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | count | count |
Chromatography:
| Chromatography ID: | CH003627 |
| Instrument Name: | Thermo Vanquish UHPLC |
| Column Name: | Merck ZIC-HILIC (2.1x100 mm, 3.5 μm) |
| Column Temperature: | 40 |
| Flow Gradient: | 0-5 min, 99% B; 5-20 min, 99-20% B; 20-21 min, 20-99% B; 21-25 min, 99% B. |
| Flow Rate: | 0.5 mL/min |
| Solvent A: | 5% acetonitrile/95% water; 10 mM ammonium acetate |
| Solvent B: | 95% acetonitrile/5% water; 10 mM ammonium acetate |
| Chromatography Type: | HILIC |
MS:
| MS ID: | MS004542 |
| Analysis ID: | AN004796 |
| Instrument Name: | Thermo Q Exactive HF-X Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | - |
| Ion Mode: | POSITIVE |
| MS ID: | MS004543 |
| Analysis ID: | AN004797 |
| Instrument Name: | Thermo Q Exactive HF-X Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | - |
| Ion Mode: | NEGATIVE |
