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The Effects of SARS-CoV-2 ORF7b on Mitochondrial Metabolism
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- Author / Creator
- Mina, Lucas
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The endoplasmic reticulum (ER) mitochondria-associated membrane (MAM), or the contact site between the ER and mitochondria, serves a control station for mitochondrial metabolism. Here, chaperones and enzymes control the Ca2+ flux between the two organelles, thereby altering energy production via mitochondrial oxidative phosphorylation. For example, the ER-localized thioredoxin-related transmembrane protein 1 (TMX1) interacts with sarco/endoplasmic reticulum Ca2+ ATPase 2b (SERCA2b) to decrease its activity. This function means that dysregulation of MAM proteins can easily disrupt energy flux, leading to increased reactive oxygen species (ROS) production and oxidative stress. In fact, dysfunctional MAMs have been observed in a variety of diseases, including viral infections. Of interest to us is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), wherein various SARS-CoV-2 proteins are known to interact with MAM proteins. In this thesis, we have characterized the interactions between the SARS-CoV-2 accessory protein ORF7b and MAM proteins. We have found that ORF7b disrupted interactions between SERCA2b and its regulators, calnexin and TMX1. Concordant with this, we observed a shift in Ca2+ equilibrium towards the mitochondria, and consequently, an increase in mitochondrial oxygen consumption and ROS production. ORF7b can therefore influence mitochondrial metabolism by targeting the MAMs.
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- Subjects / Keywords
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- Graduation date
- Spring 2023
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- Type of Item
- Thesis
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- Degree
- Master of Science
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- License
- This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.