Summary of project PR002167
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 PR002167. The data can be accessed directly via it's Project DOI: 10.21228/M8HJ9G This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002167 |
| Project DOI: | doi: 10.21228/M8HJ9G |
| Project Title: | Hypermetabolism induced pantothenate depletion in MT-ATP6 neuropathy |
| Project Summary: | Mitochondrial DNA mutations frequently result in mitochondrial dysfunction and energy deficits, compromising cellular and tissue functions. However, in some cases, bioenergetic deficits triggers a futile cycle of energy production and consumption to maintain cellular function, a phenomenon termed hypermetabolism. In this study, we used patient iPSC-derived motor neurons to investigate a truncating heteroplasmic mutation in the MT-ATP6 gene, which encodes a subunit of the proton pore of the ATP synthase. We successfully generated motor neurons with 50% mutation heteroplasmy, despite adverse effects on ATP synthase assembly. Through a combination of respirometry, metabolomic tracing, and proteomic analysis, we observed increased metabolic activity in mutant motor neurons, indicative of a hypermetabolic phenotype. This is the first study to explore hypermetabolism in neurons, revealing new significant implications of this state. This hypermetabolic state Hypermetabolism led to the reprioritization of the core metabolite acetyl-CoA and depletion of its precursor, resulting in the downregulation . We also observed the downregulation of epigenetic and SUMOylation pathways, likely as compensatory and adaptive mechanisms. Our findings suggest a link between mitochondrial dysfunction and SUMOylation, highlighting a potential new contributor to the mitochondrial hypermetabolic phenotype. |
| Institute: | University of Helsinki |
| Department: | Faculty of Medicine |
| Laboratory: | Tyynismaa lab |
| Last Name: | Torregrosa-Muñumer |
| First Name: | Rubén |
| Address: | Biomedicum Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland |
| Email: | ruben.torregrosa@helsinki.fi |
| Phone: | +358294125800 |
| Funding Source: | Academy of Finland Centre of Excellence on Stem Cell Metabolism (MetaStem), Academy of Finland Postdoctoral fellowship to RTM, and Sigrid Juselius Foundation. |
| Contributors: | Rubén Torregrosa-Muñumer, Jeremi Turkia, Jouni Kvist, Jana Pennonen, Emilia Kuuluvainen, Pekka Katajisto, Ville Hietakangas, Emil Ylikallio, Henna Tyynismaa |
Summary of all studies in project PR002167
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003523 | Hypermetabolism induced pantothenate depletion in MT-ATP6 neuropathy | Homo sapiens | University of Helsinki | MS | 2025-10-22 | 1 | 90 | Uploaded data (25.2G)* |
