| First Author | Cao X | Year | 2018 |
| Journal | Proc Natl Acad Sci U S A | Volume | 115 |
| Issue | 30 | Pages | E7063-E7072 |
| PubMed ID | 29987032 | Mgi Jnum | J:340654 |
| Mgi Id | MGI:6193236 | Doi | 10.1073/pnas.1805862115 |
| Citation | Cao X, et al. (2018) Protein moonlighting elucidates the essential human pathway catalyzing lipoic acid assembly on its cognate enzymes. Proc Natl Acad Sci U S A 115(30):E7063-E7072 |
| abstractText | The lack of attachment of lipoic acid to its cognate enzyme proteins results in devastating human metabolic disorders. These mitochondrial disorders are evident soon after birth and generally result in early death. The mutations causing specific defects in lipoyl assembly map in three genes, LIAS, LIPT1, and LIPT2 Although physiological roles have been proposed for the encoded proteins, only the LIPT1 protein had been studied at the enzyme level. LIPT1 was reported to catalyze only the second partial reaction of the classical lipoate ligase mechanism. We report that the physiologically relevant LIPT1 enzyme activity is transfer of lipoyl moieties from the H protein of the glycine cleavage system to the E2 subunits of the 2-oxoacid dehydrogenases required for respiration (e.g., pyruvate dehydrogenase) and amino acid degradation. We also report that LIPT2 encodes an octanoyl transferase that initiates lipoyl group assembly. The human pathway is now biochemically defined. |
