Summary of project PR002082
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 PR002082. The data can be accessed directly via it's Project DOI: 10.21228/M8H24R This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002082 |
| Project DOI: | doi: 10.21228/M8H24R |
| Project Title: | ADSL deficiency drives mitochondrial dysfunction and ERK2 dysregulation in a linear genotype to phenotype correlation |
| Project Summary: | Adenylosuccinate lyase (ADSL) deficiency (ADSLd) is a rare autosomal recessive defect of purine metabolism associated with a wide range of clinical manifestations. Despite ADSL implication in purine synthesis, no additional molecular alterations have been identified as a cause of ADSLd besides the accumulation of toxic substrates. Here we uncover a novel association between ADSLd and mitochondrial dysfunction, which is characterized by an increase in fragmentation and reduction in respiration and ATP production. The extent of this mitochondrial dysfunction is directly proportional to the pathological manifestations of ADSLd, which are predominantly observed in tissues that rely heavily on mitochondria. Our analysis also unveils a striking defect in mitochondrial dynamics and transport, which are associated with the suppression of ERK2 and AKT function. Remarkably, the mitochondrial phenotype can be rescued in part by overexpression of a constitutive form of ERK2 or through the administration of purine intermediates. This scenario provides an alternative explanation of ADSLd onset, reorienting research towards developing innovative therapeutic strategies based on the restoration of mitochondrial metabolism. |
| Institute: | Catholic University of the Sacred Heart |
| Last Name: | Bordi |
| First Name: | Matteo |
| Address: | Largo Francesco Vito 1, Rome, Italy, 00168, Italy |
| Email: | matteo.bordi@unicatt.it |
| Phone: | +390630155135/5258 |
Summary of all studies in project PR002082
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003347 | ADSL deficiency drives mitochondrial dysfunction and ERK2 dysregulation in a linear genotype to phenotype correlation | Homo sapiens | Catholic University of the Sacred Heart | MS | 2024-08-15 | 1 | 35 | Uploaded data (3.9G)* |
| ST003499 | Metabolic analysis of ADSL deficiency patients' EBV-LCLs. | Homo sapiens | Catholic University of the Sacred Heart | MS | 2024-10-16 | 1 | 30 | Uploaded data (1.7G)* |
