Disorders of Mitochondrial Homeostatis, Dynamics, Protein Import, and Quality Control (WP5504)
Homo sapiens
This pathway lists several genes involved in mechanisms involved in disorders of mitochondrial homeostatis, dynamics, protein import, and quality control. This pathway was inspired by Figure 46.1 of Edition 5, Chapter 46 of the book of Blau (ISBN 9783030677268). Genes linked to a disease in this book chapter are depicted in red.
Authors
Egon Willighagen and Denise SlenterActivity
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Organisms
Homo sapiensCommunities
Inherited Metabolic Disorders (IMD) Pathways Serious Request 2024 - MetaKidsAnnotations
Pathway Ontology
disease pathway mitochondrial disease pathway| Label | Type | Compact URI | Comment |
|---|---|---|---|
| arginine | Metabolite | chebi:29016 | |
| NADPH | Metabolite | chebi:16474 | cofactor to PYCR3 |
| pyrroline-5-carboxylate | Metabolite | chebi:15893 | AKA P5C |
| Proline | Metabolite | chebi:26271 | |
| biotin | Metabolite | chebi:15956 | |
| ornithine | Metabolite | chebi:18257 | |
| glutamate | Metabolite | chebi:14321 | |
| α-Ketoglutarate | Metabolite | chebi:30915 | aka 2-oxoglutaric acid |
| AFG3L2 | GeneProduct | ensembl:ENSG00000141385 | |
| AIFM1 | GeneProduct | ensembl:ENSG00000156709 | |
| AGK | GeneProduct | ensembl:ENSG00000006530 | |
| C1QBP | GeneProduct | ensembl:ENSG00000108561 | |
| CLPB | GeneProduct | ensembl:ENSG00000162129 | |
| CLPP | GeneProduct | ensembl:ENSG00000125656 | |
| DNAJC19 | GeneProduct | ensembl:ENSG00000205981 | |
| GFER | GeneProduct | hgnc.symbol:GFER | |
| HSPA9 | GeneProduct | ensembl:ENSG00000113013 | |
| HSPD1 | GeneProduct | ensembl:ENSG00000144381 | |
| HTRA2 | GeneProduct | ensembl:ENSG00000115317 | |
| LONP1 | GeneProduct | uniprot:P36776 | |
| MIPEP | GeneProduct | ensembl:ENSG00000027001 | |
| PAM16 | GeneProduct | ensembl:ENSG00000217930 | |
| PITRM1 | GeneProduct | ensembl:ENSG00000107959 | |
| PMPCA | GeneProduct | ensembl:ENSG00000165688 | |
| PMPCB | GeneProduct | ensembl:ENSG00000105819 | |
| SFXN4 | GeneProduct | ensembl:ENSG00000183605 | |
| SPG7 | GeneProduct | ensembl:ENSG00000197912 | |
| TIMM8A | GeneProduct | ensembl:ENSG00000126953 | |
| TIMM50 | GeneProduct | ensembl:ENSG00000105197 | |
| TIMMDC1 | GeneProduct | ensembl:ENSG00000113845 | |
| XPNPEP3 | GeneProduct | ensembl:ENSG00000196236 | Listed as XNPEP3 in the chapter. |
| DNM1L | GeneProduct | ensembl:ENSG00000087470 | |
| GDAP1L1 | GeneProduct | hgnc.symbol:GDAP1L1 | |
| MFF | GeneProduct | ensembl:ENSG00000168958 | |
| STAT2 | GeneProduct | ensembl:ENSG00000170581 | |
| TRAK1 | GeneProduct | ensembl:ENSG00000182606 | |
| MFN2 | GeneProduct | ensembl:ENSG00000116688 | |
| OPA1 | GeneProduct | ensembl:ENSG00000198836 | |
| SLC25A46 | GeneProduct | ensembl:ENSG00000164209 | |
| YME1L1 | GeneProduct | ensembl:ENSG00000136758 | |
| PINK1 | GeneProduct | ensembl:ENSG00000158828 | |
| PRKN | GeneProduct | ensembl:ENSG00000185345 | |
| PPA2 | GeneProduct | ensembl:ENSG00000138777 | |
| TXN2 | GeneProduct | ensembl:ENSG00000100348 | |
| TXNRD2 | GeneProduct | ensembl:ENSG00000184470 | |
| MICU1 | GeneProduct | ensembl:ENSG00000107745 | |
| ATAD3A | GeneProduct | ensembl:ENSG00000197785 | |
| MICOS13 | GeneProduct | ensembl:ENSG00000174917 | |
| UBXN1 | Protein | uniprot:Q04323 | |
| OXA1L | Protein | uniprot:Q15070 | |
| YME1L1 | Protein | uniprot:Q96TA2 | Not in Figure, but added in Table 46.35 |
| PYCR3 | Protein | uniprot:Q53H96 | Active in Cytosol |
| OPA3? | Protein | uniprot:Q9H6K4 | |
| UFD1 | Protein | uniprot:Q92890 | |
| COQ3 | Protein | uniprot:Q9NZJ6 | |
| MSTO1? | Protein | uniprot:Q9BUK6 | |
| SACS? | Protein | uniprot:Q9NZJ4 | |
| RTN4IP1 | Protein | uniprot:Q8WWV3 | also known as optic atrophy-10 (OPA10); NADPH oxidoreductase, enriched in the mitochondrial matrix of muscle tissues. DOI: https://doi.org/10.1038/s41589-023-01452-w'COQ3 was the most strongly biotinylated protein by RTN4IP1-TurboID, suggesting a potential involvement of RTN4IP1 in the CoQ production pathway within the mitochondria' DOI: https://doi.org/10.1038/s41589-023-01452-w |
| TMEM126A | Protein | uniprot:Q9H061 | |
| USP9X | Protein | uniprot:Q93008 | Ubiquitin-specific peptidase 9 X-linked'Collectively, these findings suggest that USP9x regulates the proline biosynthesis pathway and the proline cycle via PYCR3, which affects PPP and mitochondrial respiration.' DOI: https://doi.org/10.1038/s41420-024-02111-2 |
| VCP | Protein | uniprot:P55072 | |
| COQ5 | Protein | uniprot:Q5HYK3 | 'Given that we identified COQ5 as part of the interactome of RTN4IP1-TurboID, it will be intriguing to further investigate whether RTN4IP1 can assist this reaction of COQ5.' DOI: https://doi.org/10.1038/s41589-023-01452-w |
| PYCR1 | Protein | uniprot:P32322 | Active in Cytosol |
| PYCR2 | Protein | uniprot:Q96C36 | Active in Cytosol |
| OPA3 | Protein | uniprot:Q9H6K4 | |
| MSTO1 | Protein | uniprot:Q9BUK6 | |
| LONP1 | Protein | uniprot:P36776 | |
| NPLOC4 | Protein | uniprot:Q8TAT6 | AKA NPL4 |
| p47 | Protein | uniprot:P08567 | |
| MFN1 | Protein | uniprot:Q8IWA4 | |
| UBXD1/UBXN6 | Protein | uniprot:Q9BZV1 | |
| MCL1 | Protein | uniprot:Q07820 | |
| MARCHF5 | Protein | uniprot:Q9NX47 | MITOL/March5 |
References
- Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases [Internet]. Blau N, Duran M, Gibson KM, Dionisi-Vici C. Springer; 2014. 0 p. Available from: https://books.google.com/books/about/Physician_s_Guide_to_the_Diagnosis_Treat.html?hl=&id=wJRBnwEACAAJ OpenLibrary Worldcat
- Mitochondrial matrix RTN4IP1/OPA10 is an oxidoreductase for coenzyme Q synthesis. Park I, Kim KE, Kim J, Kim AK, Bae S, Jung M, et al. Nat Chem Biol. 2024 Feb;20(2):221–33. PubMed Europe PMC Scholia
- Identification of TMEM126A as OXA1L-interacting protein reveals cotranslational quality control in mitochondria. Poerschke S, Oeljeklaus S, Cruz-Zaragoza LD, Schenzielorz A, Dahal D, Hillen HS, et al. Mol Cell. 2024 Jan 18;84(2):345-358.e5. PubMed Europe PMC Scholia
- Valosin-Containing Protein (VCP): A Review of Its Diverse Molecular Functions and Clinical Phenotypes. Pontifex CS, Zaman M, Fanganiello RD, Shutt TE, Pfeffer G. Int J Mol Sci. 2024 May 22;25(11):5633. PubMed Europe PMC Scholia
- Deubiquitinase USP9x regulates the proline biosynthesis pathway in non-small cell lung cancer. Becirovic T, Zhang B, Lindskog C, Norberg E, Vakifahmetoglu-Norberg H, Kaminskyy VO, et al. Cell Death Discov. 2024 Jul 29;10(1):342. PubMed Europe PMC Scholia