Tag: apoptosis

Publication: Structural and motional changes in a cytochrome c – lipid complex implicated in apoptosis.

Congratulations to lab alum Dr. Mingyue Li and our collaborators on the publication of a new paper in the Journal of Molecular Biology. The paper is online via its DOI link. The paper describes how we used solid-state NMR spectroscopy to characterise the partial destabilization of the native fold of the protein cytochrome c, as it is bound to cardiolipin lipids. This protein-lipid complex is implicated in the process of programmed cell death, where it plays a key role in triggering the self-destruction of undesired or disease cells in higher organisms. Notably, the CL-bound protein catalyses the process of mitochondrial lipid peroxidation, which we see being reconstituted in vitro via mass-spectrometry lipidomics. The latter work is done by our longstanding collaborators in the group of Valerian Kagan at the University of Pittsburgh. The current paper builds on our earlier work, but is of especial interest based on the fact that we bridge some of our prior findings (that suggested the protein to be surprisingly “folded” on the membrane) to studies that report a greater degree of mobility of the CL-bound protein. Here we see how the experimental conditions regulate protein mobility and also pinpoint how different extents of mobility are present in the membrane-bound cytochrome c. Interestingly, the regional dynamics map partly, but not completely onto the previously identified “foldons” that define the folding landscape of this widely studied mitochondrial protein. For more details see the paper below. It is available as #openaccess so just follow the DOI link for access:


Reference:
Mingyue Li, Wanyang Sun, Vladimir A. Tyurin, Maria DeLucia, Jinwoo Ahn, Valerian E. Kagan, Patrick C.A. van der Wel (2021) Activation of Cytochrome C Peroxidase Function Through Coordinated Foldon Loop Dynamics upon Interaction with Anionic Lipids, Journal of Molecular Biology, Volume 433, Issue 15, 23 July 2021, 167057

New Publication on Lipid Oxidation

Now online in the journal Free Radical Biology and Medicine: a new review and perspective article by our collaborator Valerian Kagan (Univ. Pittsburgh). The paper (titled “Redox phospholipidomics of enzymatically generated oxygenated phospholipids as specific signals of programmed cell death”) examines the role of controlled lipid oxidation as a source of vital cellular signals. In particular it reviews recent work showing how cardiolipins and phosphatidylethanolamine lipids are oxidised by enzymes, as triggers of apoptosis and ferroptosis. Interestingly, the enzymatically generated oxidised species are distinct from those generated by spontaneous peroxidation, which may be important for the regulatory role of these species.

For more details, read the whole article here:

Kagan et al. (2020) “Redox phospholipidomics of enzymatically generated oxygenated phospholipids as specific signals of programmed cell deathFree Radical Biology and Medicine, Vol. 147, pp. 231-241