Summary of project PR001956
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 PR001956. The data can be accessed directly via it's Project DOI: 10.21228/M8WF0F This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001956 |
| Project DOI: | doi: 10.21228/M8WF0F |
| Project Title: | Muscle-type specific stress responses explain external ophthalmoplegia in mitochondrial disease |
| Project Summary: | Mitochondrial dysfunctions elicit progressive tissue-specific stress responses that can be protective or deleterious. Here, we show that even different muscles of an individual react differently to mitochondrial disease. In mitochondrial myopathy (MM), the extraocular muscles (EOMs) are affected first, followed by exercise intolerance in the large lower limb muscles. Both muscle types show clear signs of respiratory chain deficiency. However, the limbs upregulate the mitochondrial integrated stress response (ISRmt) that drives glucose carbons to anabolic repair pathways, while EOMs present no signs of ISRmt. In contrast, in EOMs, Pdk4 activation inhibits pyruvate metabolism, while beta-oxidation of fatty acids is induced - despite the reliance of beta-oxidation on a functional respiratory chain for ATP production. The data suggest that the inability to upregulate ISRmt and consequent deleterious fuel choices sensitize EOMs to early weakness and atrophy, explaining ophthalmoplegia, the most common MM sign. The distinct responses to disease even in muscles of a single individual predict different responses to treatment, which is essential knowledge when designing interventions. |
| Institute: | University of Helsinki |
| Laboratory: | Anu Wartiovaara Lab |
| Last Name: | Pradhan |
| First Name: | Swagat |
| Address: | C519b, Biomedicum 1, Haartmaninkatu 8, Helsinki, Uusimaa, 00290, Finland |
| Email: | swagat.pradhan@helsinki.fi |
| Phone: | +358465287359 |
Summary of all studies in project PR001956
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003145 | Muscle-type specific stress responses explain the onset of external ophthalmoplegia in mitochondrial disease | Mus musculus | University of Helsinki | MS | 2025-01-02 | 1 | 25 | Uploaded data (229.2M)* |
