Co-chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp60, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix. The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein.
Carbamoyl phosphate synthetase 1 (CPS1), a rate-limiting enzyme in the urea cycle, catalyzes the conversion of ammonia and bicarbonate to carbamoyl phosphate in mitochondria. Non-small cell lung carcinoma (NSCLC) cells with oncogenic KRAS and loss of the tumor suppressor LKB1 express CPS1 and depend on this enzyme for growth. CPS1 maintains pyrimidine/purine balance in these cancer cells. Silencing CPS1 reduces the pyrimidine to purine ratio and stalls DNA synthesis, leading to DNA damage and cancer cell death. In addition, the tumor suppressor p53 represses the expression of urea cycle enzymes CPS1, OTC, and ARG1 and, therefore, causes the accumulation of ammonia, suppressing cancer growth. Furthermore, research studies suggest that hypermethylation-mediated downregulation of CPS1 expression may contribute to the progression of normal hepatocytes to hepatocellular carcinoma (HCC).
The mitochondrial oxidation of long-chain fatty acids is initiated by the sequential action of carnitine palmitoyltransferase I (which is located in the outer membrane and is detergent-labile) and carnitine palmitoyltransferase II (which is located in the inner membrane and is detergent-stable), together with a carnitine-acylcarnitine translocase. CPT I is the key enzyme in the carnitine-dependent transport across the mitochondrial inner membrane and its deficiency results in a decreased rate of fatty acid beta-oxidation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.
Carnitine palmitoyltransferase-1 (CPT1), localized to the mitochondrial outer membrane, translocates fatty acids across the mitochondrial membranes and catalyzes the rate-limiting step of β-oxidation. There are three isoforms of this enzyme: CPT1A (liver), CPT1B (muscle), and CPT1C (brain). Deficiency of CPT1A results in an autosomal recessive mitochondrial fatty acid oxidation disorder. Studies have shown that physiological high blood glucose and insulin levels inhibit CPT1B activity in human muscle and therefore divert long-chain fatty acids toward storage in human muscle as triglycerides. Furthermore, mice deficient in CPT1C show less food intake and reduced body weight. These findings suggest that CPT1 may play a role in metabolic syndromes.
The protein encoded by this gene is a carboxypeptidase and bears strong sequence similarity to serine carboxypeptidases. Carboxypeptidases are a large class of proteases that act to cleave a single amino acid from the carboxy termini of proteins or peptides. The exact function of this protein, however, has not been determined.
This gene encodes a member of the retinoic acid (RA, a form of vitamin A) binding protein family and lipocalin/cytosolic fatty-acid binding protein family. The protein is a cytosol-to-nuclear shuttling protein, which facilitates RA binding to its cognate receptor complex and transfer to the nucleus. It is involved in the retinoid signaling pathway, and is associated with increased circulating low-density lipoprotein cholesterol. Alternatively spliced transcript variants encoding the same protein have been found for this gene.
Soluble retinoid carrier essential the proper function of both rod and cone photoreceptors. Participates in the regeneration of active 11-cis-retinol and 11-cis-retinaldehyde, from the inactive 11-trans products of the rhodopsin photocycle and in the de novo synthesis of these retinoids from 11-trans metabolic precursors. The cycling of retinoids between photoreceptor and adjacent pigment epithelium cells is known as the 'visual cycle'.
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