PXD024488 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Mitochondrial morphology, bioenergetics and proteomic responses in fatty acid oxidation disorders |
Description | Mutations in nuclear genes encoding for mitochondrial proteins very long-chain acyl-CoA dehydrogenase (VLCAD) and trifunctional protein (TFP) cause rare autosomal recessive disorders. Studies in fibroblasts derived from patients with mutations in VLCAD and TFP exhibit mitochondrial defects. To gain insights on pathological changes that account for the mitochondria l deficits we performed quantitative proteomic, biochemical, and morphometric analyses in fibroblasts derived from subjects with three different VLCAD and three different TFP mutations. Proteomic data that was corroborated by antibody-based detection, indicated reduced levels of VLCAD and TFP protein in cells with VLCAD and TFP mutations respectively, which in part accounted for the diminished fatty acid oxidation capacity. Decreased mitochondrial respiratory capacity in cells with VLCAD and TFP mutations was quantified after glucose removal and cells with TFP mutations had lower levels of glycogen. Despite these energetic deficiencies, the cells with VLCAD and TFP mutations did not exhibit changes in mitochondria morphology, distribution, fusion and fission, quantified by either confocal or transmission electron microscopy and corroborated by proteomic and antibody-based protein analysis. Fibroblasts with VLCAD and to a lesser extend cells with TFP mutations had increased levels of mitochondrial respiratory chain proteins and proteins that facilitate the assembly of respiratory complexes. With the exception of reduced levels of catalase and glutathione S-transferase theta-1 in cells with TFP mutations, the levels of 45 proteins across all major intracellular antioxidant networks were similar between cells with VLCAD and TFP mutations and non-disease controls. Collectively the data indicate that despite the metabolic deficits, cells with VLCAD and TFP mutations maintain their proteomic integrity to preserve cellular and mitochondria architecture, support energy production and protect against oxidative stress. |
HostingRepository | PRIDE |
AnnounceDate | 2021-03-04 |
AnnouncementXML | Submission_2021-03-03_22:23:29.667.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Hossein Fazelinia |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-03-03 01:01:01 | ID requested | |
⏵ 1 | 2021-03-03 22:23:30 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Long-chain fatty acids (LCFA), beta-oxidation, mitochondria, proteomics, very longchain acyl-CoA dehydrogenase (VLCAD), trifunctional protein (TFP) |
Contact List
Harry Ischiropoulos |
contact affiliation | Departments of Pediatrics and Systems Pharmacology and Translational Therapeutics, the Raymond and Ruth Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. |
contact email | ischirop@pennmedicine.upenn.edu |
lab head | |
Hossein Fazelinia |
contact affiliation | Children's Hospital of Philadelphia |
contact email | fazeliniah@email.chop.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD024488
- Label: PRIDE project
- Name: Mitochondrial morphology, bioenergetics and proteomic responses in fatty acid oxidation disorders