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Role of SPFH proteins in aerobic respiration of Escherichia coli
SPFH is a family of membrane proteins initially discovered in 1999 through phylogenetic analysis of stomatin proteins by Tavernarakis and colleagues. The name of this family is derived from the initials of its constituent protein groups: stomatins, prohibitins, flotillins, and HflK-HflC. All members...
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| Format: | Dissertation |
| Sprache: | Englisch |
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Philipps-Universität Marburg
2023
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| Zusammenfassung: | SPFH is a family of membrane proteins initially discovered in 1999 through phylogenetic analysis of stomatin proteins by Tavernarakis and colleagues. The name of this family is derived from the initials of its constituent protein groups: stomatins, prohibitins, flotillins, and HflK-HflC. All members within this protein family share a conserved evolutionary domain known as the SPFH domain, also referred to as the PHB (Prohibitin) domain. Since its identification, numerous SPFH proteins have been found in all three domains of life. Interestingly, all members of this family exhibit a high degree of similarity in their amino acid sequences and domain structures, which could suggest a common function across eukaryotes, archaea, and prokaryotes.
In E. coli, there are four proteins that contain the SPFH domain. These include QmcA, a stomatin protein associated with a quality control-related membrane complex, YqiK, which belongs to the flotillin group and whose function remains unknown, and the complex HflK-HflC (HflKC), responsible for modulating the activity of FtsH metalloprotease. Surprisingly, SPFH proteins have been little explored in E. coli and little is known about their functions in this model organism. In this study, we aim to systematically characterize SPFH proteins using different approaches that include localization, protein interactions, biophysical properties of the membrane, and growth under different stress conditions, among other techniques. Through these analyses, we made an interesting observation: The absence of The HflKC complex causes a growth defect that is dependent on aeration. Therefore, we focused on this phenotype to further understand its origins.
We found that the absence of HflKC complex affects the abundance of IspG, a crucial enzyme in the isoprenoid biosynthesis pathway. We elucidated a direct link between the aerobic growth defect and lack of IspG, which leads to reduced levels of ubiquinone, a molecule that plays an important role as an electron transporter in aerobic respiratory chains. Consequently, the hflKC deletion strain exhibits reduced respiration, lower ATP levels, and a decrease in membrane potential. We hypothesize that lack of IspG protein is due to FtsH protease activity. In absence of the protective cage provided by HflKC complex, IspG is more accessible, resulting in faster degradation. Further, we propose that this regulation of aerobic respiration via isoprenoid biosynthesis and ubiquinone levels might also be conserved in eukaryotic prohibitins, which could explain previously reported lack of respiration associated with prohibitin mutations in mammalian and yeast cells. |
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| DOI: | 10.17192/z2023.0681 |