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Perturbation of the yeast mitochondrial lipidome and associated membrane proteins following heterologous expression of Artemia-ANT

Scientific REPOrTS | (2018) 8:5915

Authors: Emily Chen, Michael A. Kiebish, Justice McDaniel, Katarzyna Niedzwiecka,
Roza Kucharczyk, Dora Ravasz, Fei Gao, Niven R. Narain, Rangaprasad Sarangarajan,
Thomas N. Seyfried, Vera Adam-Vizi, & Christos ChinopoulosRoberto E. Floresa, Ashley K. Browna, Luke Tausa, Julianna Khourya, Frank Glovera, Kenjiro Kamib, Rangaprasad Sarangarajanc, Tony E. Walshec, Niven R. Narainc, Michael A. Kiebishc, Laura M. Sheltonb, Christos Chinopoulosd, Thomas N. Seyfrieda

Heterologous expression is a landmark technique for studying a protein itself or its effect on
the expression host, in which membrane-embedded proteins are a common choice. Yet, the
impact of inserting a foreign protein to the lipid environment of host membranes, has never been
addressed. Here we demonstrated that heterologous expression of the Artemia franciscana adenine
nucleotide translocase (ANT) in yeasts altered lipidomic composition of their inner mitochondrial
membranes. Along with this, activities of complex II, IV and ATP synthase, all membrane-embedded
components, were significantly decreased while their expression levels remained unaffected.
Although the results represent an individual case of expressing a crustacean protein in yeast inner
mitochondrial membranes, it cannot be excluded that host lipidome alterations is a more widespread
epiphenomenon, potentially biasing heterologous expression experiments. Finally, our results raise
the possibility that not only lipids modulate protein function, but also membrane-embedded proteins
modulate lipid composition, thus revealing a reciprocal mode of regulation for these two biomolecular

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