http://www.sciencedirect.com/science/article/pii/S0014579305012895
A. Basoah, P. M. Matthews, K. J. Morten; FEBS Letters (November 2005)
Proteins are vulnerable to oxidation by reactive oxygen species (ROS), and mitochondrial proteins are especially at risk due to their proximity to ROS production. Nuclear proteins localised to mitochondria are at additional risk due to their partially unfolded state immediately after translocation.
Once proteins have been damaged, they are targeted for degradation by the cell's degradation machinery, however severe ROS damage can lead to proteins becoming harder to degrade. These undegraded proteins can then form protein aggregates which can prove toxic to the cell. Alternatively, if the protein degradation machinery is successful in destroying the damaged protein, this can lead to proteins being removed before they can be fully assembled. This can cause a deficiency of the damaged protein if it happens repeatedly.
The authors study a C2C12 myoblast cell culture and investigate the effects of ROS production on newly synthesised mitochondrial protein turnover. Cells were treated with menadione, which increased ROS production and led to an increase in protein degradation rate, which was observed using labelled methionine. Menadione levels were kept low so as not to affect cell viability (high doses have been shown to trigger cell death), but led to elevated ROS levels.
The changes in protein degradation were not uniform, and some proteins even showed decreased degradation rates. Confusingly, two different subunits of ATP synthase showed opposite effects, with one degradation rate increasing while the other decreased. The experimental timescale was not long enough to determine if these changes in degradation rates led to changes in steady-state abundance of the proteins concerned.
A. Basoah, P. M. Matthews, K. J. Morten; FEBS Letters (November 2005)
Proteins are vulnerable to oxidation by reactive oxygen species (ROS), and mitochondrial proteins are especially at risk due to their proximity to ROS production. Nuclear proteins localised to mitochondria are at additional risk due to their partially unfolded state immediately after translocation.
Once proteins have been damaged, they are targeted for degradation by the cell's degradation machinery, however severe ROS damage can lead to proteins becoming harder to degrade. These undegraded proteins can then form protein aggregates which can prove toxic to the cell. Alternatively, if the protein degradation machinery is successful in destroying the damaged protein, this can lead to proteins being removed before they can be fully assembled. This can cause a deficiency of the damaged protein if it happens repeatedly.
The authors study a C2C12 myoblast cell culture and investigate the effects of ROS production on newly synthesised mitochondrial protein turnover. Cells were treated with menadione, which increased ROS production and led to an increase in protein degradation rate, which was observed using labelled methionine. Menadione levels were kept low so as not to affect cell viability (high doses have been shown to trigger cell death), but led to elevated ROS levels.
The changes in protein degradation were not uniform, and some proteins even showed decreased degradation rates. Confusingly, two different subunits of ATP synthase showed opposite effects, with one degradation rate increasing while the other decreased. The experimental timescale was not long enough to determine if these changes in degradation rates led to changes in steady-state abundance of the proteins concerned.
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