Molecule Information

General Information of the Molecule (ID: Mol04132)

Name	Mitochondrial pyruvate carrier subunit 1 (MPC1) ,Homo sapiens
Synonyms	Brain protein 44-like protein Click to Show/Hide
Molecule Type	Protein
Gene Name	MPC1
Gene ID	51660
Location	chr6:166364919-166383013[-]
Sequence	MAGALVRKAADYVRSKDFRDYLMSTHFWGPVANWGLPIAAINDMKKSPEIISGRMTFALC CYSLTFMRFAYKVQPRNWLLFACHATNEVAQLIQGGRLIKHEMTKTASA Click to Show/Hide
Function	Mediates the uptake of pyruvate into mitochondria. . Click to Show/Hide
Uniprot ID	MPC1_HUMAN
Ensembl ID	ENSG00000060762
HGNC ID	HGNC:21606
*Click to Show/Hide the Complete Species Lineage*
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)

1 drug(s) in total

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Olaparib

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Metabolic Reprogramming via Altered Pathways (MRAP)		Click to Show/Hide
Disease Class: Non-small cell lung carcinoma [ICD-11: 2C25.Y]			[1]
Metabolic Type	Glucose metabolism
Resistant Disease	Non-small cell lung carcinoma [ICD-11: 2C25.Y]		Disease Info
Resistant Drug	Olaparib		Drug Info
Molecule Alteration	Expression	Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
In Vivo Model	Six-to 8-week-old female immunocompromised NSG mice, with KP5 cells		Mice
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Tumor volume assay
Mechanism Description	Of about 3000 genes in the screen, our data revealed that mitochondrial pyruvate carrier 1 (MPC1) is an essential factor in desensitizing nonsmall cell lung cancer (NSCLC) lung cancer lines to PARP inhibition. In contrast to NSCLC lung cancer cells, triple-negative breast cancer cells do not exhibit such desensitization following MPC1 loss and reprogram the tricarboxylic acid cycle and oxidative phosphorylation pathways to overcome PARPi treatment.

References

Ref 1	Metabolism-focused CRISPR screen unveils mitochondrial pyruvate carrier 1 as a critical driver for PARP inhibitor resistance in lung cancer. Mol Carcinog. 2024 Jun;63(6):1024-1037.