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© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Heme is an essential cofactor for multiple cellular processes in most organisms. In developing erythroid cells, the demand for heme synthesis is high, but is significantly lower in non-erythroid cells. While the biosynthesis of heme in metazoans is well understood, the tissue-specific regulation of the pathway is less explored. To better understand this, we analyzed the mitochondrial heme metabolon in erythroid and non-erythroid cell lines from the perspective of ferrochelatase (FECH), the terminal enzyme in the heme biosynthetic pathway. Affinity purification of FLAG-tagged-FECH, together with mass spectrometric analysis, was carried out to identify putative protein partners in human and murine cell lines. Proteins involved in the heme biosynthetic process and mitochondrial organization were identified as the core components of the FECH interactome. Interestingly, in non-erythroid cell lines, the FECH interactome is highly enriched with proteins associated with the tricarboxylic acid (TCA) cycle. Overall, our study shows that the mitochondrial heme metabolon in erythroid and non-erythroid cells has similarities and differences, and suggests new roles for the mitochondrial heme metabolon and heme in regulating metabolic flux and key cellular processes.

Details

Title
Proteomic Analysis of Ferrochelatase Interactome in Erythroid and Non-Erythroid Cells
Author
Chibuike David Obi 1 ; Dailey, Harry A 2 ; Jami-Alahmadi, Yasaman 3   VIAFID ORCID Logo  ; Wohlschlegel, James A 3 ; Medlock, Amy E 4   VIAFID ORCID Logo 

 Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA 
 Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA; Department of Microbiology, University of Georgia, Athens, GA 30602, USA 
 Department of Biological Chemistry, University of California Los Angeles, Los Angeles, CA 90095, USA 
 Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA; Augusta University/University of Georgia Medical Partnership, Athens, GA 30606, USA 
First page
577
Publication year
2023
Publication date
2023
Publisher
MDPI AG
e-ISSN
20751729
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2779513968
Copyright
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.