Reactome | LIAS synthesizes lipoyl-GCSH

LIAS synthesizes lipoyl-GCSH

Stable Identifier

R-HSA-6793591

Type

Reaction [transition]

Species

Homo sapiens

Compartment

mitochondrial matrix

Synonyms

LIAS:2(4Fe-4S) transforms octanoyl-K107-GCSH to lipoyl-K107-GCSH

ReviewStatus

5/5

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Mitochondrial lipoyl synthase (LIAS) mediates the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to glycine cleavage system H protein (GCSH), transforming the octanoyl moiety to a lipoyl moiety. LIAS requires two 4Fe-4S clusters as cofactors, which act as the sulfur donors in the reaction. It also requires ferredoxin FDX1 as a cofactor. Moreover, LIAS is in complex with iron-sulfur cluster scaffold NFU1, which restores the auxiliary cluster of LIAS during turnover (Morikawa et al., 2001; Warui et al., 2022; Dreishpoon et al., 2023; Joshi et al., 2023). Defects in LIAS can cause neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation (HGCLAS, MIM:614462; Mayr et al., 2011; reviewed by Cronan, 2020).

Literature References

PubMed ID	Title	Journal	Year
11389890	Do mammalian cells synthesize lipoic acid? Identification of a mouse cDNA encoding a lipoic acid synthase located in mitochondria Morikawa, T, Yasuno, R, Wada, H	FEBS Lett.	2001
37453661	FDX1 regulates cellular protein lipoylation through direct binding to LIAS Dreishpoon, MB, Bick, NR, Petrova, B, Warui, DM, Cameron, A, Booker, SJ, Kanarek, N, Golub, TR, Tsvetkov, P	J Biol Chem	2023
37481209	Lipoylation is dependent on the ferredoxin FDX1 and dispensable under hypoxia in human cells Joshi, PR, Sadre, S, Guo, XA, McCoy, JG, Mootha, VK	J Biol Chem	2023
22152680	Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation Mayr, JA, Zimmermann, FA, Fauth, C, Bergheim, C, Meierhofer, D, Radmayr, D, Zschocke, J, Koch, J, Sperl, W	Am. J. Hum. Genet.	2011
36281303	In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1 Warui, DM, Sil, D, Lee, KH, Neti, SS, Esakova, OA, Knox, HL, Krebs, C, Booker, SJ	ACS Bio Med Chem Au	2022
32508887	Progress in the Enzymology of the Mitochondrial Diseases of Lipoic Acid Requiring Enzymes Cronan, JE	Front Genet	2020