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Biochemistry PhD Seminar | Rinky Parakra

Investigation of peroxidase activity of human cytochrome c mutants

Cytochrome c has been known to be involved in the electron transfer chain for 100 years, but this mitochondrial haem protein also plays important roles in the intrinsic apoptosis pathway. During apoptosis, cytochrome c acquires a new function, peroxidase activity, leading to oxidation of cardiolipin (a mitochondrial phospholipid).

Cardiolipin oxidation is proposed to be a required step in the intrinsic apoptosis pathway. The overall aim of this thesis was to better understand the peroxidase function of cytochrome c by studying naturally occurring mutant forms of the protein that cause thromocytopenia.

Our lab has previously reported that the naturally occurring G41S and a recombinant G41T cytochrome c variant have increased peroxidase activity. The first aim of this project was to understand the reason behind increased peroxidase function of cytochrome c variants.

The results demonstrate that cytochrome c undergoes oxidation of a methionine involved in iron coordination to gain peroxidase activity. The second aim was to determine the relationship between the peroxidase activity and cardiolipin oxidation. The results show that the cytochrome c variants differ in their ability to bind to cardiolipin­‐containing liposomes and mitoplasts, resulting in differences in cardiolipin-­dependent stimulation of peroxidase activity.

Moreover, using mass spectroscopy to analyse lipid oxidation, cytochrome c-catalysed oxidation of cardiolipin was dependent on liposome composition and on the reaction conditions. In addition, when cytochrome c-­depleted mitoplasts were used, minimal cardiolipin oxidation was detected. Thus, although the cytochrome c variants are better peroxidases in vitro, the relevance of this to cardiolipin oxidation in vivo during apoptosis is still questionable. 

Date Tuesday, 21 November 2017
Time 12:00pm - 1:00pm
Event Category Health Sciences
Event Type Seminar
LocationBiochemistry seminar rm 231

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