Molecule Information

General Information of the Molecule (ID: Mol04053)

• Name: Ubiquinone (Q10) ,Homo sapiens
• Synonyms: Complex I-75kD
• Molecule Type: Protein
• Gene Name: NDUFS1
• Gene ID: 4719
• Location: chr2:206114817-206159509[-]
• Sequence:
  MLRIPVRKALVGLSKSPKGCVRTTATAASNLIEVFVDGQSVMVEPGTTVLQACEKVGMQI
  PRFCYHERLSVAGNCRMCLVEIEKAPKVVAACAMPVMKGWNILTNSEKSKKAREGVMEFL
  LANHPLDCPICDQGGECDLQDQSMMFGNDRSRFLEGKRAVEDKNIGPLVKTIMTRCIQCT
  RCIRFASEIAGVDDLGTTGRGNDMQVGTYIEKMFMSELSGNIIDICPVGALTSKPYAFTA
  RPWETRKTESIDVMDAVGSNIVVSTRTGEVMRILPRMHEDINEEWISDKTRFAYDGLKRQ
  RLTEPMVRNEKGLLTYTSWEDALSRVAGMLQSFQGKDVAAIAGGLVDAEALVALKDLLNR
  VDSDTLCTEEVFPTAGAGTDLRSNYLLNTTIAGVEEADVVLLVGTNPRFEAPLFNARIRK
  SWLHNDLKVALIGSPVDLTYTYDHLGDSPKILQDIASGSHPFSQVLKEAKKPMVVLGSSA
  LQRNDGAAILAAVSSIAQKIRMTSGVTGDWKVMNILHRIASQVAALDLGYKPGVEAIRKN
  PPKVLFLLGADGGCITRQDLPKDCFIIYQGHHGDVGAPIADVILPGAAYTEKSATYVNTE
  GRAQQTKVAVTPPGLAREDWKIIRALSEIAGMTLPYDTLDQVRNRLEEVSPNLVRYDDIE
  GANYFQQANELSKLVNQQLLADPLVPPQLTIKDFYMTDSISRASQTMAKCVKAVTEGAQA
  VEEPSIC
• 3D-structure: PDB ID: 5XTB; Classification: Oxidoreductase/electron transport; Method: Electron microscopy; Resolution: 3.40 Å
• Function: Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:30879903, PubMed:31557978). Essential for catalysing the entry and efficient transfer of electrons within complex I (PubMed:31557978). Plays a key role in the assembly and stability of complex I and participates in the association of complex I with ubiquinol-cytochrome reductase complex (Complex III) to form supercomplexes (PubMed:30879903, PubMed:31557978). .
• Uniprot ID: NDUS1_HUMAN
• Ensembl ID: ENSG00000023228
• HGNC ID: HGNC:7707

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Bortezomib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Multiple myeloma [ICD-11: 2A83.0] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Multiple myeloma [ICD-11: 2A83.0]
• Resistant Drug: Bortezomib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: AMO-1 cells; Blood; Homo sapiens (Human); CVCL_1806
• In Vitro Model: ARH-77 cells; Peripheral blood; Homo sapiens (Human); CVCL_1072
• In Vitro Model: MM RPMI-8226 cells; Blood; Homo sapiens (Human); CVCL_0014
• Experiment for Molecule Alteration: Proteomics
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Mechanistically, BTZ-resistant cells show increased activity of glutamine-driven TCA cycle and oxidative phosphorylation, together with an increased vulnerability towards ETC inhibition. Moreover, BTZ resistance is accompanied by high levels of the mitochondrial electron carrier CoQ, while the mevalonate pathway inhibitor simvastatin increases cell death and decreases CoQ levels, specifically in BTZ-resistant cells. Both in vitro and in vivo, simvastatin enhances the effect of bortezomib treatment. Our study links CoQ synthesis to drug resistance in MM and provides a novel avenue for improving BTZ responses through statin-induced inhibition of mitochondrial metabolism.

Simvastatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Multiple myeloma [ICD-11: 2A83.0] [1]

• Metabolic Type: Lipid metabolism
• Sensitive Disease: Multiple myeloma [ICD-11: 2A83.0]
• Sensitive Drug: Simvastatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: AMO-1 cells; Blood; Homo sapiens (Human); CVCL_1806
• In Vitro Model: ARH-77 cells; Peripheral blood; Homo sapiens (Human); CVCL_1072
• In Vitro Model: MM RPMI-8226 cells; Blood; Homo sapiens (Human); CVCL_0014
• Experiment for Molecule Alteration: Proteomics
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Mechanistically, BTZ-resistant cells show increased activity of glutamine-driven TCA cycle and oxidative phosphorylation, together with an increased vulnerability towards ETC inhibition. Moreover, BTZ resistance is accompanied by high levels of the mitochondrial electron carrier CoQ, while the mevalonate pathway inhibitor simvastatin increases cell death and decreases CoQ levels, specifically in BTZ-resistant cells. Both in vitro and in vivo, simvastatin enhances the effect of bortezomib treatment. Our study links CoQ synthesis to drug resistance in MM and provides a novel avenue for improving BTZ responses through statin-induced inhibition of mitochondrial metabolism.

References

• Ref 1: Targeting coenzyme Q10 synthesis overcomes bortezomib resistance in multiple myeloma. Mol Omics. 2022 Jan 17;18(1):19-30.