Universität zu Köln

Mellis, Anna-Theresa ORCID: 0000-0002-2027-8750, Misko, Albert L., Arjune, Sita ORCID: 0000-0002-6121-4614, Liang, Ye, Erdelyi, Katalin, Ditroi, Tamas, Kaczmarek, Alexander T., Nagy, Peter and Schwarz, Guenter ORCID: 0000-0002-2118-9338 (2021). The role of glutamate oxaloacetate transaminases in sulfite biosynthesis and H2S metabolism. Redox Biol., 38. AMSTERDAM: ELSEVIER. ISSN 2213-2317

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Abstract

Molybdenum cofactor deficiency and isolated sulfite oxidase deficiency are two rare genetic disorders that are caused by impairment of the mitochondrial enzyme sulfite oxidase. Sulfite oxidase is catalyzing the terminal reaction of cellular cysteine catabolism, the oxidation of sulfite to sulfate. Absence of sulfite oxidase leads to the accumulation of sulfite, which has been identified as a cellular toxin. However, the molecular pathways leading to the production of sulfite are still not completely understood. In order to identify novel treatment options for both disorders, the understanding of cellular cysteine catabolism - and its alterations upon loss of sulfite oxidase - is of utmost importance. Here we applied a new detection method of sulfite in cellular extracts to dissect the contribution of cytosolic and mitochondrial glutamate oxaloacetate transaminase (GOT) in the transformation of cysteine sulfinic acid to sulfite and pyruvate. We found that the cytosolic isoform GOT1 is primarily responsible for the production of sulfite. Moreover, loss of sulfite oxidase activity results in the accumulation of sulfite, H2S and persulfidated cysteine and glutathione, which is consistent with an increase of SQR protein levels. Surprisingly, none of the known H2S-producing pathways were found to be upregulated under conditions of sulfite toxicity suggesting an alternative route of sulfite-induced shift from oxidative to H2S dependent cysteine catabolism.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mellis, Anna-Theresa UNSPECIFIED orcid.org/0000-0002-2027-8750 UNSPECIFIED Misko, Albert L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Arjune, Sita UNSPECIFIED orcid.org/0000-0002-6121-4614 UNSPECIFIED Liang, Ye UNSPECIFIED UNSPECIFIED UNSPECIFIED Erdelyi, Katalin UNSPECIFIED UNSPECIFIED UNSPECIFIED Ditroi, Tamas UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaczmarek, Alexander T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nagy, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarz, Guenter UNSPECIFIED orcid.org/0000-0002-2118-9338 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-592788
DOI:	10.1016/j.redox.2020.101800
Journal or Publication Title:	Redox Biol.
Volume:	38
Date:	2021
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	2213-2317
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MOLYBDENUM COFACTOR DEFICIENCY; HYDROGEN-SULFIDE; ASPARTATE-AMINOTRANSFERASE; CYSTEINE AMINOTRANSFERASE; OXIDATIVE STRESS; SULFANE SULFUR; PURIFICATION; DIOXYGENASE; BRAIN; ETHE1 Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59278